rs2276278

Variant names:

• chr11-77161123-G-A
• rs2276278
• NM_000260.4:c.1343+8G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-77161123-G-A
• chr11-77161123-G-T
• chr11-77161123-G-C

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.1343+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 1,613,482 control chromosomes in the GnomAD database, including 6,123 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (971 hom., cov: 32)
  • Exomes 𝑓: 0.072 (5152 hom.)
• Consequence: MYO7A NM_000260.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002743
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -1.40
• Publications: 8 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=-0.9).
• BP6: Variant 11-77161123-G-A is Benign according to our data. Variant chr11-77161123-G-A is described in ClinVar as Benign. ClinVar VariationId is 43142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 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.1343+8G>A		splice_region intron	N/A	NP_000251.3	Q13402-1
	MYO7A	NM_001127180.2		c.1343+8G>A		splice_region intron	N/A	NP_001120652.1	Q13402-2
	MYO7A	NM_001369365.1		c.1310+8G>A		splice_region 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.1343+8G>A		splice_region intron	N/A	ENSP00000386331.3	Q13402-1
	MYO7A	ENST00000458637.6	TSL:1	c.1343+8G>A		splice_region intron	N/A	ENSP00000392185.2	Q13402-2
	MYO7A	ENST00000409619.6	TSL:1	c.1310+8G>A		splice_region intron	N/A	ENSP00000386635.2	Q13402-8

Frequencies

GnomAD3 genomes AF: 0.0997 AC: 15169 AN: 152116 Hom.: 967 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0465

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0552

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.0966 AC: 24045 AN: 249004 AF XY: 0.0916

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.0853

Gnomad EAS exome AF: 0.270

Gnomad FIN exome AF: 0.0449

Gnomad NFE exome AF: 0.0552

Gnomad OTH exome AF: 0.0859

GnomAD4 exome AF: 0.0720 AC: 105237 AN: 1461248 Hom.: 5152 Cov.: 32 AF XY: 0.0719 AC XY: 52236 AN XY: 726870

African (AFR) AF: 0.173 AC: 5777 AN: 33472

American (AMR) AF: 0.139 AC: 6226 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.0856 AC: 2235 AN: 26122

East Asian (EAS) AF: 0.279 AC: 11057 AN: 39694

South Asian (SAS) AF: 0.0938 AC: 8087 AN: 86248

European-Finnish (FIN) AF: 0.0450 AC: 2403 AN: 53398

Middle Eastern (MID) AF: 0.0997 AC: 575 AN: 5766

European-Non Finnish (NFE) AF: 0.0573 AC: 63682 AN: 1111504

Other (OTH) AF: 0.0861 AC: 5195 AN: 60346

GnomAD4 genome AF: 0.0998 AC: 15186 AN: 152234 Hom.: 971 Cov.: 32 AF XY: 0.100 AC XY: 7449 AN XY: 74430

African (AFR) AF: 0.165 AC: 6843 AN: 41530

American (AMR) AF: 0.103 AC: 1578 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0859 AC: 298 AN: 3468

East Asian (EAS) AF: 0.270 AC: 1396 AN: 5172

South Asian (SAS) AF: 0.101 AC: 489 AN: 4822

European-Finnish (FIN) AF: 0.0465 AC: 493 AN: 10606

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0552 AC: 3757 AN: 68014

Other (OTH) AF: 0.103 AC: 217 AN: 2114

Alfa AF: 0.0715 Hom.: 741

Bravo AF: 0.111

Asia WGS AF: 0.186 AC: 646 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Autosomal dominant nonsyndromic hearing loss 11 (2)
-	-	2	Autosomal recessive nonsyndromic hearing loss 2 (2)
-	-	2	not provided (2)
-	-	2	Usher syndrome type 1 (2)
-	-	1	Usher syndrome type 1B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.021
DANN	Benign	0.75
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000027
dbscSNV1_RF	Benign	0.0
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: rs2276278; hg19: chr11-76872169; COSMIC: COSV68684024;