rs72933642

chr11-77198633-C-Gchr11-77198633-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000260.4(MYO7A):c.4568+12C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00669 in 1,613,342 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0091 ( 47 hom., cov: 33)

Exomes 𝑓: 0.0064 ( 145 hom. )

Consequence

MYO7A
NM_000260.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.239

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-77198633-C-G is Benign according to our data. Variant chr11-77198633-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 43246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77198633-C-G is described in Lovd as [Benign]. Variant chr11-77198633-C-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00915 (1393/152308) while in subpopulation EAS AF= 0.0133 (69/5182). AF 95% confidence interval is 0.0108. There are 47 homozygotes in gnomad4. There are 939 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO7A	NM_000260.4 linkuse as main transcript	c.4568+12C>G		intron_variant		ENST00000409709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO7A	ENST00000409709.9 linkuse as main transcript	c.4568+12C>G		intron_variant		1	NM_000260.4		Q13402-1

Frequencies

GnomAD3 genomes

AF:

0.00916

AC:

1394

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.0135

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0882

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00489

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.0107

AC:

2649

AN:

247750

Hom.:

AF XY:

0.0106

AC XY:

1431

AN XY:

134574

show subpopulations

Gnomad AFR exome

AF:

0.000652

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.0136

Gnomad SAS exome

AF:

0.00233

Gnomad FIN exome

AF:

0.0794

Gnomad NFE exome

AF:

0.00476

Gnomad OTH exome

AF:

0.00847

GnomAD4 exome

AF:

0.00644

AC:

9403

AN:

1461034

Hom.:

145

Cov.:

AF XY:

0.00624

AC XY:

4532

AN XY:

726754

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00126

Gnomad4 EAS exome

AF:

0.0100

Gnomad4 SAS exome

AF:

0.00280

Gnomad4 FIN exome

AF:

0.0704

Gnomad4 NFE exome

AF:

0.00413

Gnomad4 OTH exome

AF:

0.00539

GnomAD4 genome

AF:

0.00915

AC:

1393

AN:

152308

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

939

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.0133

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0882

Gnomad4 NFE

AF:

0.00489

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00371

Hom.:

Bravo

AF:

0.00307

Asia WGS

AF:

0.00895

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 05, 2015

c.4568+12C>G in intron 34 of MYO7A: This variant is not expected to have clinica l significance because it is not located within the conserved splice consensus s equence. It has been identified in 8.6% (546/6314) of Finnish European chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs72933642). -

Autosomal dominant nonsyndromic hearing loss 11

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Autosomal recessive nonsyndromic hearing loss 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

Usher syndrome type 1

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

7.7

Dann

Benign

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over