chr11-77207277-T-C

Variant names:

• chr11-77207277-T-C
• rs2276291
• NM_000260.4:c.5743-12T>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.5743-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,592,366 control chromosomes in the GnomAD database, including 273,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30386 hom., cov: 31)
  • Exomes 𝑓: 0.58 (242842 hom.)
• Consequence: MYO7A NM_000260.4 intron
• Scores: Splicing: ADA: 0.0001877
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.401
• Publications: 14 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=-0.96).
• BP6: Variant 11-77207277-T-C is Benign according to our data. Variant chr11-77207277-T-C is described in ClinVar as Benign. ClinVar VariationId is 43297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 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.5743-12T>C		intron	N/A	NP_000251.3	Q13402-1
	MYO7A	NM_001127180.2		c.5629-12T>C		intron	N/A	NP_001120652.1	Q13402-2
	MYO7A	NM_001369365.1		c.5596-12T>C		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.5743-12T>C		intron	N/A	ENSP00000386331.3	Q13402-1
	MYO7A	ENST00000458637.6	TSL:1	c.5629-12T>C		intron	N/A	ENSP00000392185.2	Q13402-2
	MYO7A	ENST00000409619.6	TSL:1	c.5596-12T>C		intron	N/A	ENSP00000386635.2	Q13402-8

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95216 AN: 151836 Hom.: 30330 Cov.: 31

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.634

GnomAD2 exomes AF: 0.589 AC: 132727 AN: 225270 AF XY: 0.577

Gnomad AFR exome AF: 0.738

Gnomad AMR exome AF: 0.692

Gnomad ASJ exome AF: 0.530

Gnomad EAS exome AF: 0.508

Gnomad FIN exome AF: 0.656

Gnomad NFE exome AF: 0.585

Gnomad OTH exome AF: 0.579

GnomAD4 exome AF: 0.577 AC: 831602 AN: 1440412 Hom.: 242842 Cov.: 30 AF XY: 0.573 AC XY: 409855 AN XY: 715568

African (AFR) AF: 0.737 AC: 24334 AN: 33036

American (AMR) AF: 0.688 AC: 29282 AN: 42574

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 13543 AN: 25740

East Asian (EAS) AF: 0.483 AC: 18775 AN: 38900

South Asian (SAS) AF: 0.444 AC: 37083 AN: 83582

European-Finnish (FIN) AF: 0.656 AC: 34164 AN: 52050

Middle Eastern (MID) AF: 0.603 AC: 3387 AN: 5620

European-Non Finnish (NFE) AF: 0.579 AC: 636811 AN: 1099284

Other (OTH) AF: 0.574 AC: 34223 AN: 59626

GnomAD4 genome AF: 0.627 AC: 95342 AN: 151954 Hom.: 30386 Cov.: 31 AF XY: 0.628 AC XY: 46614 AN XY: 74268

African (AFR) AF: 0.733 AC: 30365 AN: 41436

American (AMR) AF: 0.649 AC: 9911 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1854 AN: 3470

East Asian (EAS) AF: 0.488 AC: 2510 AN: 5146

South Asian (SAS) AF: 0.431 AC: 2069 AN: 4806

European-Finnish (FIN) AF: 0.658 AC: 6952 AN: 10572

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39607 AN: 67928

Other (OTH) AF: 0.632 AC: 1337 AN: 2114

Alfa AF: 0.597 Hom.: 7018

Bravo AF: 0.634

Asia WGS AF: 0.467 AC: 1625 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Autosomal dominant nonsyndromic hearing loss 11 (2)
-	-	2	Autosomal recessive nonsyndromic hearing loss 2 (2)
-	-	2	Usher syndrome type 1 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.51
DANN	Benign	0.45
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.010
SpliceAI score (max)		0.020		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: rs2276291; hg19: chr11-76918322;