11-77174355-G-C

Variant names:

• chr11-77174355-G-C
• rs948970
• NM_000260.4:c.1936-401G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000260.4(MYO7A):​c.1936-401G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,078 control chromosomes in the GnomAD database, including 27,636 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (27636 hom., cov: 32)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
• Usher syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, PanelApp Australia
• Usher syndrome type 1B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant nonsyndromic hearing loss 11

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Usher syndrome type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.1936-401G>C		intron_variant	Intron 16 of 48	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.1936-401G>C		intron_variant	Intron 16 of 48	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.1936-401G>C		intron_variant	Intron 16 of 48	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.1903-401G>C		intron_variant	Intron 17 of 49	1		ENSP00000386635.2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90510 AN: 151960 Hom.: 27598 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.573

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.596 AC: 90605 AN: 152078 Hom.: 27636 Cov.: 32 AF XY: 0.596 AC XY: 44312 AN XY: 74318

African (AFR) AF: 0.716 AC: 29682 AN: 41468

American (AMR) AF: 0.628 AC: 9603 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1378 AN: 3470

East Asian (EAS) AF: 0.456 AC: 2346 AN: 5144

South Asian (SAS) AF: 0.352 AC: 1695 AN: 4814

European-Finnish (FIN) AF: 0.645 AC: 6828 AN: 10592

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37275 AN: 67978

Other (OTH) AF: 0.571 AC: 1207 AN: 2114

Alfa AF: 0.575 Hom.: 3207

Bravo AF: 0.605

Asia WGS AF: 0.432 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.010
DANN	Benign	0.65
PhyloP100		-2.6
PromoterAI		0.0037	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs948970; hg19: chr11-76885401;