rs2276278

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000409709.9(MYO7A):c.1343+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 1,613,482 control chromosomes in the GnomAD database, including 6,123 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 971 hom., cov: 32)

Exomes 𝑓: 0.072 ( 5152 hom. )

Consequence

MYO7A
ENST00000409709.9 splice_region, intron

Scores

Splicing: ADA: 0.00002743

Clinical Significance

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

Conservation

PhyloP100: -1.40

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=-0.9).

BP6

Variant 11-77161123-G-A is Benign according to our data. Variant chr11-77161123-G-A is described in ClinVar as [Benign]. Clinvar id is 43142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77161123-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4 linkuse as main transcript	c.1343+8G>A		splice_region_variant, intron_variant		ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9 linkuse as main transcript	c.1343+8G>A	splice_region_variant, intron_variant	1	NM_000260.4	ENSP00000386331		Q13402-1
MYO7A	ENST00000409619.6 linkuse as main transcript	c.1310+8G>A	splice_region_variant, intron_variant	1		ENSP00000386635		Q13402-8
MYO7A	ENST00000458637.6 linkuse as main transcript	c.1343+8G>A	splice_region_variant, intron_variant	1		ENSP00000392185	P1	Q13402-2

Frequencies

GnomAD3 genomes

AF:

0.0997

AC:

15169

AN:

152116

Hom.:

967

Cov.:

show subpopulations

Gnomad AFR

AF:

0.165

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0859

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0465

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.0552

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.0966

AC:

24045

AN:

249004

Hom.:

1710

AF XY:

0.0916

AC XY:

12374

AN XY:

135094

show subpopulations

Gnomad AFR exome

AF:

0.170

Gnomad AMR exome

AF:

0.147

Gnomad ASJ exome

AF:

0.0853

Gnomad EAS exome

AF:

0.270

Gnomad SAS exome

AF:

0.0961

Gnomad FIN exome

AF:

0.0449

Gnomad NFE exome

AF:

0.0552

Gnomad OTH exome

AF:

0.0859

GnomAD4 exome

AF:

0.0720

AC:

105237

AN:

1461248

Hom.:

5152

Cov.:

AF XY:

0.0719

AC XY:

52236

AN XY:

726870

show subpopulations

Gnomad4 AFR exome

AF:

0.173

Gnomad4 AMR exome

AF:

0.139

Gnomad4 ASJ exome

AF:

0.0856

Gnomad4 EAS exome

AF:

0.279

Gnomad4 SAS exome

AF:

0.0938

Gnomad4 FIN exome

AF:

0.0450

Gnomad4 NFE exome

AF:

0.0573

Gnomad4 OTH exome

AF:

0.0861

GnomAD4 genome

AF:

0.0998

AC:

15186

AN:

152234

Hom.:

971

Cov.:

AF XY:

0.100

AC XY:

7449

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.165

Gnomad4 AMR

AF:

0.103

Gnomad4 ASJ

AF:

0.0859

Gnomad4 EAS

AF:

0.270

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.0465

Gnomad4 NFE

AF:

0.0552

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0665

Hom.:

480

Bravo

AF:

0.111

Asia WGS

AF:

0.186

AC:

646

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 27, 2013	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 13, 2008	c.1343+8G>A in intron 12 of MYO7A: This variant is not expected to have clinical significance because It has also been identified in 28% (2399/8596) of East Asi an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs2276278). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Autosomal recessive nonsyndromic hearing loss 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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 dominant nonsyndromic hearing loss 11

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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 12, 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 provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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

-0.90

CADD

Benign

0.021

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.0

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