chr11-77194559-G-T

Variant names:

Variant summary

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

The NM_000260.4(MYO7A):c.4323+35G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,548,086 control chromosomes in the GnomAD database, including 231,942 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26133 hom., cov: 33)

Exomes 𝑓: 0.54 ( 205809 hom. )

Consequence

MYO7A
NM_000260.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.45

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=-0.91).

BP6

Variant 11-77194559-G-T is Benign according to our data. Variant chr11-77194559-G-T is described in ClinVar as [Benign]. Clinvar id is 255663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-77194559-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4 link	c.4323+35G>T		intron_variant	Intron 32 of 48	ENST00000409709.9	NP_000251.3	Q13402-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO7A	ENST00000409709.9 link	c.4323+35G>T	intron_variant	Intron 32 of 48	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 link	c.4323+35G>T	intron_variant	Intron 32 of 48	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 link	c.4290+35G>T	intron_variant	Intron 33 of 49	1		ENSP00000386635.2	Q13402-8
MYO7A	ENST00000458169.2 link	c.1866+35G>T	intron_variant	Intron 12 of 28	1		ENSP00000417017.2	H7C4D8
MYO7A	ENST00000670577.1 link	n.2163+35G>T	intron_variant	Intron 15 of 31			ENSP00000499323.1	A0A590UJ94

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88169

AN:

151898

Hom.:

26081

Cov.:

show subpopulations

Gnomad AFR

AF:

0.678

Gnomad AMI

AF:

0.498

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.465

Gnomad SAS

AF:

0.347

Gnomad FIN

AF:

0.625

Gnomad MID

AF:

0.471

Gnomad NFE

AF:

0.541

Gnomad OTH

AF:

0.576

GnomAD3 exomes

AF:

0.549

AC:

89870

AN:

163652

Hom.:

25287

AF XY:

0.534

AC XY:

46134

AN XY:

86354

show subpopulations

Gnomad AFR exome

AF:

0.681

Gnomad AMR exome

AF:

0.666

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.483

Gnomad SAS exome

AF:

0.374

Gnomad FIN exome

AF:

0.630

Gnomad NFE exome

AF:

0.549

Gnomad OTH exome

AF:

0.522

GnomAD4 exome

AF:

0.539

AC:

753101

AN:

1396068

Hom.:

205809

Cov.:

AF XY:

0.533

AC XY:

367176

AN XY:

688278

show subpopulations

Gnomad4 AFR exome

AF:

0.675

Gnomad4 AMR exome

AF:

0.658

Gnomad4 ASJ exome

AF:

0.405

Gnomad4 EAS exome

AF:

0.473

Gnomad4 SAS exome

AF:

0.372

Gnomad4 FIN exome

AF:

0.623

Gnomad4 NFE exome

AF:

0.546

Gnomad4 OTH exome

AF:

0.522

GnomAD4 genome

AF:

0.581

AC:

88289

AN:

152018

Hom.:

26133

Cov.:

AF XY:

0.581

AC XY:

43200

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.678

Gnomad4 AMR

AF:

0.624

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.465

Gnomad4 SAS

AF:

0.348

Gnomad4 FIN

AF:

0.625

Gnomad4 NFE

AF:

0.541

Gnomad4 OTH

AF:

0.573

Alfa

AF:

0.543

Hom.:

19148

Bravo

AF:

0.590

Asia WGS

AF:

0.436

AC:

1519

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 2

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 11

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.021

DANN

Benign

0.65

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