rs2276290

chr11-77207452-G-A

Variant summary

Our verdict is Benign. Variant got -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:5

Conservation

PhyloP100: -0.743

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=-0.89).

BP6

Variant 11-77207452-G-A is Benign according to our data. Variant chr11-77207452-G-A is described in ClinVar 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 Lovd as [Benign].

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/exons	MANE	UniProt
MYO7A	NM_000260.4 linkuse as main transcript	c.5856+50G>A		intron_variant		ENST00000409709.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO7A	ENST00000409709.9 linkuse as main transcript	c.5856+50G>A		intron_variant		1	NM_000260.4		Q13402-1

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

GnomAD3 exomes

AF:

0.561

AC:

95601

AN:

170476

Hom.:

27408

AF XY:

0.550

AC XY:

49666

AN XY:

90382

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 SAS exome

AF:

0.410

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

Gnomad4 AFR exome

AF:

0.539

Gnomad4 AMR exome

AF:

0.664

Gnomad4 ASJ exome

AF:

0.521

Gnomad4 EAS exome

AF:

0.480

Gnomad4 SAS exome

AF:

0.413

Gnomad4 FIN exome

AF:

0.649

Gnomad4 NFE exome

AF:

0.565

Gnomad4 OTH exome

AF:

0.549

GnomAD4 genome

AF:

0.561

AC:

85277

AN:

151990

Hom.:

24124

Cov.:

AF XY:

0.563

AC XY:

41799

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.541

Gnomad4 AMR

AF:

0.621

Gnomad4 ASJ

AF:

0.528

Gnomad4 EAS

AF:

0.484

Gnomad4 SAS

AF:

0.395

Gnomad4 FIN

AF:

0.649

Gnomad4 NFE

AF:

0.564

Gnomad4 OTH

AF:

0.575

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive nonsyndromic hearing loss 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Autosomal dominant nonsyndromic hearing loss 11

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Usher syndrome type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

Cadd

Benign

4.9

Dann

Benign

0.41

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