17-75618714-C-T

Variant names:

• chr17-75618714-C-T
• rs1093994
• NM_001395058.1:c.6988-429C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395058.1(MYO15B):​c.6988-429C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,132 control chromosomes in the GnomAD database, including 6,107 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 (6107 hom., cov: 33)
• Consequence: MYO15B NM_001395058.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO15B	NM_001395058.1	c.6988-429C>T		intron_variant	Intron 43 of 63	ENST00000645453.3	NP_001381987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO15B	ENST00000645453.3	c.6988-429C>T		intron_variant	Intron 43 of 63		NM_001395058.1	ENSP00000495242.3

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42272 AN: 152014 Hom.: 6109 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.278 AC: 42274 AN: 152132 Hom.: 6107 Cov.: 33 AF XY: 0.274 AC XY: 20338 AN XY: 74354

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.290

Alfa AF: 0.215 Hom.: 678

Bravo AF: 0.274

Asia WGS AF: 0.165 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.65
DANN	Benign	0.49

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: rs1093994; hg19: chr17-73614794;