17-75620008-T-C

Variant names:

• chr17-75620008-T-C
• rs820152
• NM_001395058.1:c.7431T>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001395058.1(MYO15B):​c.7431T>C​(p.Asn2477Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 701,504 control chromosomes in the GnomAD database, including 42,581 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8655 hom., cov: 34)
  • Exomes 𝑓: 0.34 (33926 hom.)
• Consequence: MYO15B NM_001395058.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706

Genes affected

MYO15B (HGNC:14083): (myosin XVB) Predicted to enable ATP binding activity; actin binding activity; and cytoskeletal motor activity. Predicted to be located in brush border; cytoplasm; and cytoskeleton. Predicted to be part of myosin complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-0.706 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO15B	NM_001395058.1	c.7431T>C	p.Asn2477Asn	synonymous_variant	Exon 47 of 64	ENST00000645453.3	NP_001381987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO15B	ENST00000645453.3	c.7431T>C	p.Asn2477Asn	synonymous_variant	Exon 47 of 64		NM_001395058.1	ENSP00000495242.3

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50520 AN: 152048 Hom.: 8657 Cov.: 34

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.348

GnomAD3 exomes AF: 0.322 AC: 44268 AN: 137508 Hom.: 7638 AF XY: 0.323 AC XY: 24081 AN XY: 74498

Gnomad AFR exome AF: 0.288

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.157

Gnomad SAS exome AF: 0.263

Gnomad FIN exome AF: 0.365

Gnomad NFE exome AF: 0.377

Gnomad OTH exome AF: 0.364

GnomAD4 exome AF: 0.344 AC: 188971 AN: 549338 Hom.: 33926 Cov.: 0 AF XY: 0.341 AC XY: 101527 AN XY: 297356

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.488

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.368

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.332 AC: 50527 AN: 152166 Hom.: 8655 Cov.: 34 AF XY: 0.328 AC XY: 24372 AN XY: 74372

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.294

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.345

Alfa AF: 0.354 Hom.: 6277

Bravo AF: 0.329

Asia WGS AF: 0.204 AC: 713 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.22
DANN	Benign	0.53

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

LitVar

Other links and lift over

dbSNP: rs820152; hg19: chr17-73616088; COSMIC: COSV73824616; COSMIC: COSV73824616;