NM_000260.4:c.5856+50G>A

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.5856+50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 1,327,794 control chromosomes in the GnomAD database, including 208,644 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 24124 hom., cov: 32)

Exomes 𝑓: 0.56 ( 184520 hom. )

Consequence

MYO7A
NM_000260.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.743

Publications

11 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=-0.89).

BP6

Variant 11-77207452-G-A is Benign according to our data. Variant chr11-77207452-G-A is described in CliVar as Benign. Clinvar id is 255664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77207452-G-A is described in CliVar as Benign. Clinvar id is 255664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77207452-G-A is described in CliVar as Benign. Clinvar id is 255664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77207452-G-A is described in CliVar as Benign. Clinvar id is 255664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77207452-G-A is described in CliVar as Benign. Clinvar id is 255664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77207452-G-A is described in CliVar as Benign. Clinvar id is 255664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77207452-G-A is described in CliVar as Benign. Clinvar id is 255664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77207452-G-A is described in CliVar as Benign. Clinvar id is 255664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77207452-G-A is described in CliVar as Benign. Clinvar id is 255664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4 link	c.5856+50G>A		intron_variant	Intron 42 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.5856+50G>A	intron_variant	Intron 42 of 48	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 link	c.5742+50G>A	intron_variant	Intron 42 of 48	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 link	c.5709+50G>A	intron_variant	Intron 43 of 49	1		ENSP00000386635.2	Q13402-8
MYO7A	ENST00000458169.2 link	c.3282+50G>A	intron_variant	Intron 22 of 28	1		ENSP00000417017.2	H7C4D8
MYO7A	ENST00000670577.1 link	n.*454+50G>A	intron_variant	Intron 25 of 31			ENSP00000499323.1	A0A590UJ94

Frequencies

GnomAD3 genomes

AF:

0.561

AC:

85176

AN:

151872

Hom.:

24084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.603

Gnomad AMR

AF:

0.620

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.483

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.649

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.576

GnomAD2 exomes

AF:

0.561

AC:

95601

AN:

170476

AF XY:

0.550

show subpopulations

Gnomad AFR exome

AF:

0.529

Gnomad AMR exome

AF:

0.670

Gnomad ASJ exome

AF:

0.524

Gnomad EAS exome

AF:

0.507

Gnomad FIN exome

AF:

0.650

Gnomad NFE exome

AF:

0.567

Gnomad OTH exome

AF:

0.557

GnomAD4 exome

AF:

0.558

AC:

655674

AN:

1175804

Hom.:

184520

Cov.:

AF XY:

0.552

AC XY:

326654

AN XY:

591464

show subpopulations

African (AFR)

AF:

0.539

AC:

14620

AN:

27134

American (AMR)

AF:

0.664

AC:

24086

AN:

36258

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

12412

AN:

23828

East Asian (EAS)

AF:

0.480

AC:

16951

AN:

35304

South Asian (SAS)

AF:

0.413

AC:

30983

AN:

74936

European-Finnish (FIN)

AF:

0.649

AC:

32320

AN:

49804

Middle Eastern (MID)

AF:

0.575

AC:

3028

AN:

5266

European-Non Finnish (NFE)

AF:

0.565

AC:

493346

AN:

872440

Other (OTH)

AF:

0.549

AC:

27928

AN:

50834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

14378

28756

43135

57513

71891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12598

25196

37794

50392

62990

<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:

0.561

AC:

85277

AN:

151990

Hom.:

24124

Cov.:

AF XY:

0.563

AC XY:

41799

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.541

AC:

22412

AN:

41452

American (AMR)

AF:

0.621

AC:

9489

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

1834

AN:

3472

East Asian (EAS)

AF:

0.484

AC:

2477

AN:

5120

South Asian (SAS)

AF:

0.395

AC:

1902

AN:

4810

European-Finnish (FIN)

AF:

0.649

AC:

6873

AN:

10582

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.564

AC:

38352

AN:

67964

Other (OTH)

AF:

0.575

AC:

1212

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1929

3858

5788

7717

9646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<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:

0.564

Hom.:

4470

Bravo

AF:

0.562

Asia WGS

AF:

0.437

AC:

1521

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 13, 2018

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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 2

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 11

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 1

Benign:1

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

-0.89

CADD

Benign

4.9

(source)

DANN

Benign

0.41

PhyloP100

-0.74

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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