rs2276291

Variant names:

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.5743-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,592,366 control chromosomes in the GnomAD database, including 273,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30386 hom., cov: 31)

Exomes 𝑓: 0.58 ( 242842 hom. )

Consequence

MYO7A
NM_000260.4 intron

Scores

Splicing: ADA: 0.0001877

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.401

Publications

14 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=-0.96).

BP6

Variant 11-77207277-T-C is Benign according to our data. Variant chr11-77207277-T-C is described in ClinVar as Benign. ClinVar VariationId is 43297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4 link	c.5743-12T>C		intron_variant	Intron 41 of 48	ENST00000409709.9	NP_000251.3	Q13402-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO7A	ENST00000409709.9 link	c.5743-12T>C	intron_variant	Intron 41 of 48	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 link	c.5629-12T>C	intron_variant	Intron 41 of 48	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 link	c.5596-12T>C	intron_variant	Intron 42 of 49	1		ENSP00000386635.2	Q13402-8
MYO7A	ENST00000458169.2 link	c.3169-12T>C	intron_variant	Intron 21 of 28	1		ENSP00000417017.2	H7C4D8
MYO7A	ENST00000670577.1 link	n.*341-12T>C	intron_variant	Intron 24 of 31			ENSP00000499323.1	A0A590UJ94

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

95216

AN:

151836

Hom.:

30330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.732

Gnomad AMI

AF:

0.608

Gnomad AMR

AF:

0.648

Gnomad ASJ

AF:

0.534

Gnomad EAS

AF:

0.487

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.658

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.634

GnomAD2 exomes

AF:

0.589

AC:

132727

AN:

225270

AF XY:

0.577

show subpopulations

Gnomad AFR exome

AF:

0.738

Gnomad AMR exome

AF:

0.692

Gnomad ASJ exome

AF:

0.530

Gnomad EAS exome

AF:

0.508

Gnomad FIN exome

AF:

0.656

Gnomad NFE exome

AF:

0.585

Gnomad OTH exome

AF:

0.579

GnomAD4 exome

AF:

0.577

AC:

831602

AN:

1440412

Hom.:

242842

Cov.:

AF XY:

0.573

AC XY:

409855

AN XY:

715568

show subpopulations

African (AFR)

AF:

0.737

AC:

24334

AN:

33036

American (AMR)

AF:

0.688

AC:

29282

AN:

42574

Ashkenazi Jewish (ASJ)

AF:

0.526

AC:

13543

AN:

25740

East Asian (EAS)

AF:

0.483

AC:

18775

AN:

38900

South Asian (SAS)

AF:

0.444

AC:

37083

AN:

83582

European-Finnish (FIN)

AF:

0.656

AC:

34164

AN:

52050

Middle Eastern (MID)

AF:

0.603

AC:

3387

AN:

5620

European-Non Finnish (NFE)

AF:

0.579

AC:

636811

AN:

1099284

Other (OTH)

AF:

0.574

AC:

34223

AN:

59626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

17497

34993

52490

69986

87483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17508

35016

52524

70032

87540

<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:

0.627

AC:

95342

AN:

151954

Hom.:

30386

Cov.:

AF XY:

0.628

AC XY:

46614

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.733

AC:

30365

AN:

41436

American (AMR)

AF:

0.649

AC:

9911

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.534

AC:

1854

AN:

3470

East Asian (EAS)

AF:

0.488

AC:

2510

AN:

5146

South Asian (SAS)

AF:

0.431

AC:

2069

AN:

4806

European-Finnish (FIN)

AF:

0.658

AC:

6952

AN:

10572

Middle Eastern (MID)

AF:

0.626

AC:

184

AN:

294

European-Non Finnish (NFE)

AF:

0.583

AC:

39607

AN:

67928

Other (OTH)

AF:

0.632

AC:

1337

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1807

3614

5422

7229

9036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.597

Hom.:

7018

Bravo

AF:

0.634

Asia WGS

AF:

0.467

AC:

1625

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 23, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

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

- -

Mar 03, 2015

GeneDx

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.51

(source)

DANN

Benign

0.45

PhyloP100

-0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00019

dbscSNV1_RF

Benign

0.010

SpliceAI score (max)

0.020

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