11-77208423-A-T

Variant names:

• chr11-77208423-A-T
• rs1320703
• NM_000260.4:c.5857-7A>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.5857-7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,593,946 control chromosomes in the GnomAD database, including 253,876 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 0.56 (24040 hom., cov: 33)
  • Exomes 𝑓: 0.56 (229836 hom.)
• Consequence: MYO7A NM_000260.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003007
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -0.0280
• Publications: 18 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=-0.93).
• BP6: Variant 11-77208423-A-T is Benign according to our data. Variant chr11-77208423-A-T is described in ClinVar as Benign. ClinVar VariationId is 43303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.611 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.5857-7A>T		splice_region intron	N/A	NP_000251.3	Q13402-1
	MYO7A	NM_001127180.2		c.5743-7A>T		splice_region intron	N/A	NP_001120652.1	Q13402-2
	MYO7A	NM_001369365.1		c.5710-7A>T		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.5857-7A>T		splice_region intron	N/A	ENSP00000386331.3	Q13402-1
	MYO7A	ENST00000458637.6	TSL:1	c.5743-7A>T		splice_region intron	N/A	ENSP00000392185.2	Q13402-2
	MYO7A	ENST00000409619.6	TSL:1	c.5710-7A>T		splice_region intron	N/A	ENSP00000386635.2	Q13402-8

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85030 AN: 151642 Hom.: 24002 Cov.: 33

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.579

GnomAD2 exomes AF: 0.562 AC: 137338 AN: 244336 AF XY: 0.553

Gnomad AFR exome AF: 0.515

Gnomad AMR exome AF: 0.674

Gnomad ASJ exome AF: 0.521

Gnomad EAS exome AF: 0.505

Gnomad FIN exome AF: 0.648

Gnomad NFE exome AF: 0.569

Gnomad OTH exome AF: 0.559

GnomAD4 exome AF: 0.561 AC: 808682 AN: 1442188 Hom.: 229836 Cov.: 31 AF XY: 0.557 AC XY: 399825 AN XY: 717988

African (AFR) AF: 0.519 AC: 17147 AN: 33010

American (AMR) AF: 0.670 AC: 29611 AN: 44196

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 13503 AN: 26002

East Asian (EAS) AF: 0.481 AC: 19037 AN: 39542

South Asian (SAS) AF: 0.427 AC: 36505 AN: 85488

European-Finnish (FIN) AF: 0.651 AC: 34637 AN: 53170

Middle Eastern (MID) AF: 0.582 AC: 3330 AN: 5722

European-Non Finnish (NFE) AF: 0.568 AC: 622024 AN: 1095338

Other (OTH) AF: 0.551 AC: 32888 AN: 59720

GnomAD4 genome AF: 0.561 AC: 85129 AN: 151758 Hom.: 24040 Cov.: 33 AF XY: 0.563 AC XY: 41715 AN XY: 74148

African (AFR) AF: 0.525 AC: 21754 AN: 41400

American (AMR) AF: 0.621 AC: 9487 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1831 AN: 3470

East Asian (EAS) AF: 0.483 AC: 2480 AN: 5138

South Asian (SAS) AF: 0.411 AC: 1978 AN: 4808

European-Finnish (FIN) AF: 0.652 AC: 6859 AN: 10518

Middle Eastern (MID) AF: 0.610 AC: 177 AN: 290

European-Non Finnish (NFE) AF: 0.572 AC: 38799 AN: 67854

Other (OTH) AF: 0.578 AC: 1214 AN: 2102

Alfa AF: 0.568 Hom.: 7962

Bravo AF: 0.561

Asia WGS AF: 0.444 AC: 1545 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Autosomal dominant nonsyndromic hearing loss 11 (2)
-	-	2	Autosomal recessive nonsyndromic hearing loss 2 (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	-0.93
CADD	Benign	2.5
DANN	Benign	0.79
PhyloP100		-0.028
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000030
dbscSNV1_RF	Benign	0.0080
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: rs1320703; hg19: chr11-76919468; COSMIC: COSV68684425; COSMIC: COSV68684425;