11-77208423-A-T

Position:

chr11-77208423-A-T

Variant summary

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

The NM_000260.4(MYO7A):c.5857-7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,593,946 control chromosomes in the GnomAD database, including 253,876 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 0.56 ( 24040 hom., cov: 33)

Exomes 𝑓: 0.56 ( 229836 hom. )

Consequence

MYO7A
NM_000260.4 splice_region, intron

Scores

Splicing: ADA: 0.00003007

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.0280

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:

MYO7A (HGNC:):

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=-0.93).

BP6

Variant 11-77208423-A-T is Benign according to our data. Variant chr11-77208423-A-T is described in ClinVar as [Benign]. Clinvar id is 43303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77208423-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.611 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.5857-7A>T		splice_region_variant, intron_variant		ENST00000409709.9	NP_000251.3	Q13402-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MYO7A	ENST00000409709.9 linkuse as main transcript	c.5857-7A>T	splice_region_variant, intron_variant	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 linkuse as main transcript	c.5743-7A>T	splice_region_variant, intron_variant	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 linkuse as main transcript	c.5710-7A>T	splice_region_variant, intron_variant	1		ENSP00000386635.2	Q13402-8
MYO7A	ENST00000458169.2 linkuse as main transcript	c.3283-7A>T	splice_region_variant, intron_variant	1		ENSP00000417017.2	H7C4D8
MYO7A	ENST00000670577.1 linkuse as main transcript	n.*455-7A>T	splice_region_variant, intron_variant			ENSP00000499323.1	A0A590UJ94

Frequencies

GnomAD3 genomes

AF:

0.561

AC:

85030

AN:

151642

Hom.:

24002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.525

Gnomad AMI

AF:

0.604

Gnomad AMR

AF:

0.621

Gnomad ASJ

AF:

0.528

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.652

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.572

Gnomad OTH

AF:

0.579

GnomAD3 exomes

AF:

0.562

AC:

137338

AN:

244336

Hom.:

39040

AF XY:

0.553

AC XY:

73298

AN XY:

132486

show subpopulations

Gnomad AFR exome

AF:

0.515

Gnomad AMR exome

AF:

0.674

Gnomad ASJ exome

AF:

0.521

Gnomad EAS exome

AF:

0.505

Gnomad SAS exome

AF:

0.421

Gnomad FIN exome

AF:

0.648

Gnomad NFE exome

AF:

0.569

Gnomad OTH exome

AF:

0.559

GnomAD4 exome

AF:

0.561

AC:

808682

AN:

1442188

Hom.:

229836

Cov.:

AF XY:

0.557

AC XY:

399825

AN XY:

717988

show subpopulations

Gnomad4 AFR exome

AF:

0.519

Gnomad4 AMR exome

AF:

0.670

Gnomad4 ASJ exome

AF:

0.519

Gnomad4 EAS exome

AF:

0.481

Gnomad4 SAS exome

AF:

0.427

Gnomad4 FIN exome

AF:

0.651

Gnomad4 NFE exome

AF:

0.568

Gnomad4 OTH exome

AF:

0.551

GnomAD4 genome

AF:

0.561

AC:

85129

AN:

151758

Hom.:

24040

Cov.:

AF XY:

0.563

AC XY:

41715

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.525

Gnomad4 AMR

AF:

0.621

Gnomad4 ASJ

AF:

0.528

Gnomad4 EAS

AF:

0.483

Gnomad4 SAS

AF:

0.411

Gnomad4 FIN

AF:

0.652

Gnomad4 NFE

AF:

0.572

Gnomad4 OTH

AF:

0.578

Alfa

AF:

0.568

Hom.:

7962

Bravo

AF:

0.561

Asia WGS

AF:

0.444

AC:

1545

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 08, 2007	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 19, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive nonsyndromic hearing loss 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
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. -

Autosomal dominant nonsyndromic hearing loss 11

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
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. -

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	- -

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

-0.93

CADD

Benign

2.5

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000030

dbscSNV1_RF

Benign

0.0080

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