rs2276283

Variant names:

• chr11-77174733-G-A
• rs2276283
• NM_000260.4:c.1936-23G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-77174733-G-A
• chr11-77174733-G-C
• chr11-77174733-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000260.4(MYO7A):​c.1936-23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,557,772 control chromosomes in the GnomAD database, including 226,220 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (21056 hom., cov: 33)
  • Exomes 𝑓: 0.54 (205164 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0280
• Publications: 11 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 Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Usher syndrome type 1

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

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

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-77174733-G-A is Benign according to our data. Variant chr11-77174733-G-A is described in ClinVar as Benign. ClinVar VariationId is 255661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	NM_000260.4	MANE Select	c.1936-23G>A		intron	N/A	NP_000251.3	Q13402-1
	MYO7A	NM_001127180.2		c.1936-23G>A		intron	N/A	NP_001120652.1	Q13402-2
	MYO7A	NM_001369365.1		c.1903-23G>A		intron	N/A	NP_001356294.1	Q13402-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO7A	ENST00000409709.9	TSL:1 MANE Select	c.1936-23G>A		intron	N/A	ENSP00000386331.3	Q13402-1
	MYO7A	ENST00000458637.6	TSL:1	c.1936-23G>A		intron	N/A	ENSP00000392185.2	Q13402-2
	MYO7A	ENST00000409619.6	TSL:1	c.1903-23G>A		intron	N/A	ENSP00000386635.2	Q13402-8

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79436 AN: 151934 Hom.: 21049 Cov.: 33

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.519

GnomAD2 exomes AF: 0.528 AC: 90162 AN: 170746 AF XY: 0.515

Gnomad AFR exome AF: 0.469

Gnomad AMR exome AF: 0.646

Gnomad ASJ exome AF: 0.399

Gnomad EAS exome AF: 0.478

Gnomad FIN exome AF: 0.636

Gnomad NFE exome AF: 0.546

Gnomad OTH exome AF: 0.504

GnomAD4 exome AF: 0.537 AC: 755049 AN: 1405720 Hom.: 205164 Cov.: 39 AF XY: 0.532 AC XY: 369113 AN XY: 694134

African (AFR) AF: 0.463 AC: 14894 AN: 32184

American (AMR) AF: 0.638 AC: 23749 AN: 37202

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 9917 AN: 25282

East Asian (EAS) AF: 0.465 AC: 17021 AN: 36604

South Asian (SAS) AF: 0.382 AC: 30617 AN: 80046

European-Finnish (FIN) AF: 0.634 AC: 29661 AN: 46798

Middle Eastern (MID) AF: 0.401 AC: 2142 AN: 5336

European-Non Finnish (NFE) AF: 0.551 AC: 597503 AN: 1083860

Other (OTH) AF: 0.506 AC: 29545 AN: 58408

GnomAD4 genome AF: 0.523 AC: 79467 AN: 152052 Hom.: 21056 Cov.: 33 AF XY: 0.526 AC XY: 39085 AN XY: 74348

African (AFR) AF: 0.469 AC: 19455 AN: 41456

American (AMR) AF: 0.597 AC: 9130 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1370 AN: 3466

East Asian (EAS) AF: 0.455 AC: 2348 AN: 5156

South Asian (SAS) AF: 0.358 AC: 1728 AN: 4824

European-Finnish (FIN) AF: 0.644 AC: 6803 AN: 10570

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.544 AC: 36955 AN: 67968

Other (OTH) AF: 0.517 AC: 1093 AN: 2114

Alfa AF: 0.508 Hom.: 3600

Bravo AF: 0.522

Asia WGS AF: 0.420 AC: 1461 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 11 (1)
-	-	1	Autosomal recessive nonsyndromic hearing loss 2 (1)
-	-	1	not specified (1)
-	-	1	Usher syndrome type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.68
PhyloP100		0.028
PromoterAI		-0.055	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: rs2276283; hg19: chr11-76885779; COSMIC: COSV68684715; COSMIC: COSV68684715;