rs948970

Positions:

• chr11-77174355-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.1936-401G>C		intron_variant		ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.1936-401G>C		intron_variant		1	NM_000260.4	ENSP00000386331
MYO7A	ENST00000409619.6	c.1903-401G>C		intron_variant		1		ENSP00000386635
MYO7A	ENST00000458637.6	c.1936-401G>C		intron_variant		1		ENSP00000392185	P1

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

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.571

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

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

Other links and lift over

dbSNP: rs948970; hg19: chr11-76885401;