rs820186

chr17-75623840-G-A

Variant summary

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

The NM_001395058.1(MYO15B):c.8142G>A(p.Thr2714=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 699,066 control chromosomes in the GnomAD database, including 30,753 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 0.28 (6063 hom., cov: 32)
  • Exomes 𝑓: 0.29 (24690 hom.)
• Consequence: MYO15B NM_001395058.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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=-0.63).
• BP7: Synonymous conserved (PhyloP=-1.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO15B	NM_001395058.1	c.8142G>A	p.Thr2714=	synonymous_variant	54/64	ENST00000645453.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO15B	ENST00000645453.3	c.8142G>A	p.Thr2714=	synonymous_variant	54/64		NM_001395058.1	P1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 42173 AN: 148254 Hom.: 6065 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.300

GnomAD3 exomes AF: 0.268 AC: 36632 AN: 136718 Hom.: 5343 AF XY: 0.270 AC XY: 20066 AN XY: 74276

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.187

Gnomad ASJ exome AF: 0.399

Gnomad EAS exome AF: 0.153

Gnomad SAS exome AF: 0.211

Gnomad FIN exome AF: 0.305

Gnomad NFE exome AF: 0.328

Gnomad OTH exome AF: 0.309

GnomAD4 exome AF: 0.291 AC: 160380 AN: 550696 Hom.: 24690 Cov.: 0 AF XY: 0.289 AC XY: 86111 AN XY: 298136

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.194

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.306

Gnomad4 NFE exome AF: 0.326

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome AF: 0.284 AC: 42173 AN: 148370 Hom.: 6063 Cov.: 32 AF XY: 0.281 AC XY: 20285 AN XY: 72064

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.298

Alfa AF: 0.319 Hom.: 2369

Bravo AF: 0.274

Asia WGS AF: 0.170 AC: 594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	1.6
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs820186; hg19: chr17-73619920; COSMIC: COSV58640829; COSMIC: COSV58640829;