17-18118293-G-A

Variant names:

• chr17-18118293-G-A
• rs712267
• NM_016239.4:c.-219-289G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016239.4(MYO15A):​c.-219-289G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,940 control chromosomes in the GnomAD database, including 17,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (17996 hom., cov: 32)
• Consequence: MYO15A NM_016239.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.327

Genes affected

MYO15A (HGNC:7594): (myosin XVA) This gene encodes an unconventional myosin. This protein differs from other myosins in that it has a long N-terminal extension preceding the conserved motor domain. Studies in mice suggest that this protein is necessary for actin organization in the hair cells of the cochlea. Mutations in this gene have been associated with profound, congenital, neurosensory, nonsyndromal deafness. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Read-through transcripts containing an upstream gene and this gene have been identified, but they are not thought to encode a fusion protein. Several alternatively spliced transcript variants have been described, but their full length sequences have not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 17-18118293-G-A is Benign according to our data. Variant chr17-18118293-G-A is described in ClinVar as [Benign]. Clinvar id is 1261079.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO15A	NM_016239.4	c.-219-289G>A		intron_variant	Intron 1 of 65	ENST00000647165.2	NP_057323.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO15A	ENST00000647165.2	c.-219-289G>A		intron_variant	Intron 1 of 65		NM_016239.4	ENSP00000495481.1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70177 AN: 151822 Hom.: 17948 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.434

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.463 AC: 70279 AN: 151940 Hom.: 17996 Cov.: 32 AF XY: 0.472 AC XY: 35074 AN XY: 74252

African (AFR) AF: 0.654 AC: 27087 AN: 41424

American (AMR) AF: 0.485 AC: 7403 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1454 AN: 3470

East Asian (EAS) AF: 0.637 AC: 3278 AN: 5144

South Asian (SAS) AF: 0.706 AC: 3398 AN: 4814

European-Finnish (FIN) AF: 0.415 AC: 4387 AN: 10560

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21853 AN: 67930

Other (OTH) AF: 0.433 AC: 915 AN: 2114

Alfa AF: 0.368 Hom.: 3053

Bravo AF: 0.471

Asia WGS AF: 0.661 AC: 2296 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.18
PhyloP100		-0.33
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

Publications

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Other links and lift over

dbSNP: rs712267; hg19: chr17-18021607; COSMIC: COSV52764444; COSMIC: COSV52764444;