rs150114658

Variant names:

• chr11-77162337-C-T
• rs150114658
• NM_000260.4:c.1554+7C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-77162337-C-T
• chr11-77162337-C-A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS1

The NM_000260.4(MYO7A):​c.1554+7C>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 0.000176 in 1,551,128 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: MYO7A NM_000260.4 splice_region, intron
• Scores: Splicing: ADA: 0.0002842
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:6
• Conservation: PhyloP100: -0.162
• Publications: 1 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 11-77162337-C-T is Benign according to our data. Variant chr11-77162337-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 178480.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000854 (130/152312) while in subpopulation AFR AF = 0.00284 (118/41568). AF 95% confidence interval is 0.00242. There are 0 homozygotes in GnomAd4. There are 64 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.1554+7C>T		splice_region intron	N/A	NP_000251.3	Q13402-1
	MYO7A	NM_001127180.2		c.1554+7C>T		splice_region intron	N/A	NP_001120652.1	Q13402-2
	MYO7A	NM_001369365.1		c.1521+7C>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.1554+7C>T		splice_region intron	N/A	ENSP00000386331.3	Q13402-1
	MYO7A	ENST00000458637.6	TSL:1	c.1554+7C>T		splice_region intron	N/A	ENSP00000392185.2	Q13402-2
	MYO7A	ENST00000409619.6	TSL:1	c.1521+7C>T		splice_region intron	N/A	ENSP00000386635.2	Q13402-8

Frequencies

GnomAD3 genomes AF: 0.000867 AC: 132 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000161 AC: 25 AN: 155424 AF XY: 0.000146

Gnomad AFR exome AF: 0.00226

Gnomad AMR exome AF: 0.000162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000102 AC: 143 AN: 1398816 Hom.: 0 Cov.: 31 AF XY: 0.0000768 AC XY: 53 AN XY: 689938

African (AFR) AF: 0.00266 AC: 84 AN: 31576

American (AMR) AF: 0.000224 AC: 8 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.000114 AC: 9 AN: 79194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5296

European-Non Finnish (NFE) AF: 0.0000204 AC: 22 AN: 1078894

Other (OTH) AF: 0.000345 AC: 20 AN: 57948

GnomAD4 genome AF: 0.000854 AC: 130 AN: 152312 Hom.: 0 Cov.: 33 AF XY: 0.000859 AC XY: 64 AN XY: 74474

African (AFR) AF: 0.00284 AC: 118 AN: 41568

American (AMR) AF: 0.000588 AC: 9 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000530 Hom.: 0

Bravo AF: 0.000892

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 11 (1)
-	1	-	Autosomal recessive nonsyndromic hearing loss 2 (1)
-	-	1	MYO7A-related disorder (1)
-	-	1	not provided (1)
-	1	-	Usher syndrome type 1 (1)
-	-	1	Usher syndrome type 1B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	6.3
DANN	Benign	0.82
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00028
dbscSNV1_RF	Benign	0.050
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: rs150114658; hg19: chr11-76873383;