rs2276278

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000260.4(MYO7A):c.1343+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 1,613,482 control chromosomes in the GnomAD database, including 6,123 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 971 hom., cov: 32)

Exomes 𝑓: 0.072 ( 5152 hom. )

Consequence

MYO7A
NM_000260.4 splice_region, intron

Scores

Splicing: ADA: 0.00002743

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -1.40

Publications

8 publications found

Variant links:

Genes affected

MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

MYO7A Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive nonsyndromic hearing loss 2
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
Usher syndrome type 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, PanelApp Australia
Usher syndrome type 1B
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal dominant nonsyndromic hearing loss 11
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Usher syndrome type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MYO7A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 11-77161123-G-A is Benign according to our data. Variant chr11-77161123-G-A is described in ClinVar as Benign. ClinVar VariationId is 43142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4 link	c.1343+8G>A		splice_region_variant, intron_variant	Intron 12 of 48	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
MYO7A	ENST00000409709.9 link	c.1343+8G>A	splice_region_variant, intron_variant	Intron 12 of 48	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6 link	c.1343+8G>A	splice_region_variant, intron_variant	Intron 12 of 48	1		ENSP00000392185.2
MYO7A	ENST00000409619.6 link	c.1310+8G>A	splice_region_variant, intron_variant	Intron 13 of 49	1		ENSP00000386635.2

Frequencies

GnomAD3 genomes

AF:

0.0997

AC:

15169

AN:

152116

Hom.:

967

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0859

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0465

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.0552

Gnomad OTH

AF:

0.103

GnomAD2 exomes

AF:

0.0966

AC:

24045

AN:

249004

AF XY:

0.0916

show subpopulations

Gnomad AFR exome

AF:

0.170

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.0853

Gnomad EAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.0449

Gnomad NFE exome

AF:

0.0552

Gnomad OTH exome

AF:

0.0859

GnomAD4 exome

AF:

0.0720

AC:

105237

AN:

1461248

Hom.:

5152

Cov.:

AF XY:

0.0719

AC XY:

52236

AN XY:

726870

show subpopulations

African (AFR)

AF:

0.173

AC:

5777

AN:

33472

American (AMR)

AF:

0.139

AC:

6226

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.0856

AC:

2235

AN:

26122

East Asian (EAS)

AF:

0.279

AC:

11057

AN:

39694

South Asian (SAS)

AF:

0.0938

AC:

8087

AN:

86248

European-Finnish (FIN)

AF:

0.0450

AC:

2403

AN:

53398

Middle Eastern (MID)

AF:

0.0997

AC:

575

AN:

5766

European-Non Finnish (NFE)

AF:

0.0573

AC:

63682

AN:

1111504

Other (OTH)

AF:

0.0861

AC:

5195

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

4719

9437

14156

18874

23593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2722

5444

8166

10888

13610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0998

AC:

15186

AN:

152234

Hom.:

971

Cov.:

AF XY:

0.100

AC XY:

7449

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.165

AC:

6843

AN:

41530

American (AMR)

AF:

0.103

AC:

1578

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0859

AC:

298

AN:

3468

East Asian (EAS)

AF:

0.270

AC:

1396

AN:

5172

South Asian (SAS)

AF:

0.101

AC:

489

AN:

4822

European-Finnish (FIN)

AF:

0.0465

AC:

493

AN:

10606

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0552

AC:

3757

AN:

68014

Other (OTH)

AF:

0.103

AC:

217

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

675

1350

2025

2700

3375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0715

Hom.:

741

Bravo

AF:

0.111

Asia WGS

AF:

0.186

AC:

646

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 27, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 13, 2008

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.1343+8G>A in intron 12 of MYO7A: This variant is not expected to have clinical significance because It has also been identified in 28% (2399/8596) of East Asi an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs2276278). -

May 22, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 2

Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal dominant nonsyndromic hearing loss 11

Benign:2

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Usher syndrome type 1

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Usher syndrome type 1B

Benign:1

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.021

(source)

DANN

Benign

0.75

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over