rs759572835

Variant names:

• chr11-77190879-GCCCGGAAGCACCTCCT-G
• rs759572835
• NM_000260.4:c.3924+31_3924+46delAAGCACCTCCTCCCGG

Your query was ambiguous. Multiple possible variants found:

• chr11-77190879-GCCCGGAAGCACCTCCT-G
• chr11-77190879-GCCCGGAAGCACCTCCT-GCCCGGAAGCACCTCCTCCCGGAAGCACCTCCT
• chr11-77190879-GCCCGGAAGCACCTCCT-GCCCGGAAGCACCTCCTCCCGGAAGCACCTCCTCCCGGAAGCACCTCCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000260.4(MYO7A):​c.3924+31_3924+46delAAGCACCTCCTCCCGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000844 in 1,548,072 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (3 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.09

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 -10 ACMG points.

• BP6: Variant 11-77190879-GCCCGGAAGCACCTCCT-G is Benign according to our data. Variant chr11-77190879-GCCCGGAAGCACCTCCT-G is described in ClinVar as [Benign]. Clinvar id is 1166129.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-77190879-GCCCGGAAGCACCTCCT-G is described in Lovd as [Likely_benign]. Variant chr11-77190879-GCCCGGAAGCACCTCCT-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00218 (332/152216) while in subpopulation AFR AF= 0.0058 (241/41544). AF 95% confidence interval is 0.0052. There are 3 homozygotes in gnomad4. There are 168 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4	c.3924+31_3924+46delAAGCACCTCCTCCCGG		intron_variant	Intron 30 of 48	ENST00000409709.9	NP_000251.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO7A	ENST00000409709.9	c.3924+31_3924+46delAAGCACCTCCTCCCGG		intron_variant	Intron 30 of 48	1	NM_000260.4	ENSP00000386331.3
MYO7A	ENST00000458637.6	c.3924+31_3924+46delAAGCACCTCCTCCCGG		intron_variant	Intron 30 of 48	1		ENSP00000392185.2
MYO7A	ENST00000409619.6	c.3891+31_3891+46delAAGCACCTCCTCCCGG		intron_variant	Intron 31 of 49	1		ENSP00000386635.2
MYO7A	ENST00000458169.2	c.1467+31_1467+46delAAGCACCTCCTCCCGG		intron_variant	Intron 10 of 28	1		ENSP00000417017.2
MYO7A	ENST00000670577.1	n.1764+31_1764+46delAAGCACCTCCTCCCGG		intron_variant	Intron 13 of 31			ENSP00000499323.1

Frequencies

GnomAD3 genomes AF: 0.00214 AC: 326 AN: 152098 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00567

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00290

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.000891 AC: 152 AN: 170654 Hom.: 1 AF XY: 0.000777 AC XY: 71 AN XY: 91402

Gnomad AFR exome AF: 0.00424

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00190

Gnomad EAS exome AF: 0.00344

Gnomad SAS exome AF: 0.000221

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000306

Gnomad OTH exome AF: 0.000439

GnomAD4 exome AF: 0.000698 AC: 974 AN: 1395856 Hom.: 3 AF XY: 0.000673 AC XY: 462 AN XY: 686204

Gnomad4 AFR exome AF: 0.00631

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.00211

Gnomad4 EAS exome AF: 0.00854

Gnomad4 SAS exome AF: 0.000202

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000218

Gnomad4 OTH exome AF: 0.00173

GnomAD4 genome AF: 0.00218 AC: 332 AN: 152216 Hom.: 3 Cov.: 32 AF XY: 0.00226 AC XY: 168 AN XY: 74414

Gnomad4 AFR AF: 0.00580

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.000817 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Usher syndrome type 1B Benign:1

Jul 01, 2021

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs759572835; hg19: chr11-76901924;