rs11237123

Positions:

chr11-77211901-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000260.4(MYO7A):c.6318G>A(p.Lys2106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,613,528 control chromosomes in the GnomAD database, including 32,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5062 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27832 hom. )

Consequence

MYO7A
NM_000260.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.83

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 11-77211901-G-A is Benign according to our data. Variant chr11-77211901-G-A is described in ClinVar as [Benign]. Clinvar id is 43324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77211901-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.84 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO7A	NM_000260.4 linkuse as main transcript	c.6318G>A	p.Lys2106=	synonymous_variant	46/49	ENST00000409709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO7A	ENST00000409709.9 linkuse as main transcript	c.6318G>A	p.Lys2106=	synonymous_variant	46/49	1	NM_000260.4		Q13402-1

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36306

AN:

152050

Hom.:

5033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.369

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.0671

Gnomad SAS

AF:

0.0855

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.230

GnomAD3 exomes

AF:

0.177

AC:

44183

AN:

249168

Hom.:

4719

AF XY:

0.176

AC XY:

23798

AN XY:

135144

show subpopulations

Gnomad AFR exome

AF:

0.368

Gnomad AMR exome

AF:

0.0981

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.0695

Gnomad SAS exome

AF:

0.0873

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.201

Gnomad OTH exome

AF:

0.180

GnomAD4 exome

AF:

0.188

AC:

274288

AN:

1461360

Hom.:

27832

Cov.:

AF XY:

0.185

AC XY:

134769

AN XY:

726982

show subpopulations

Gnomad4 AFR exome

AF:

0.382

Gnomad4 AMR exome

AF:

0.103

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.0459

Gnomad4 SAS exome

AF:

0.0893

Gnomad4 FIN exome

AF:

0.266

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.185

GnomAD4 genome

AF:

0.239

AC:

36389

AN:

152168

Hom.:

5062

Cov.:

AF XY:

0.240

AC XY:

17853

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.370

Gnomad4 AMR

AF:

0.149

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.0672

Gnomad4 SAS

AF:

0.0852

Gnomad4 FIN

AF:

0.293

Gnomad4 NFE

AF:

0.202

Gnomad4 OTH

AF:

0.229

Alfa

AF:

0.207

Hom.:

2847

Bravo

AF:

0.234

Asia WGS

AF:

0.104

AC:

361

AN:

3478

EpiCase

AF:

0.209

EpiControl

AF:

0.204

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal dominant nonsyndromic hearing loss 11

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

Autosomal recessive nonsyndromic hearing loss 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

Usher syndrome type 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 08, 2007

- -

Usher syndrome type 1B

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

9.4

DANN

Benign

0.81

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