chr17-75618714-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395058.1. 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
	MYO15B	NM_001395058.1	MANE Select	c.6988-429C>T		intron	N/A	NP_001381987.1	Q96JP2-1
	MYO15B	NM_001309242.2		c.6874-429C>T		intron	N/A	NP_001296171.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO15B	ENST00000645453.3	MANE Select	c.6988-429C>T		intron	N/A	ENSP00000495242.3	Q96JP2-1
	MYO15B	ENST00000642007.2		c.2545-429C>T		intron	N/A	ENSP00000492911.2	A0A286YF23
	MYO15B	ENST00000577342.5	TSL:5	n.*311-429C>T		intron	N/A	ENSP00000488316.1	A0A0J9YXA6

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

African (AFR) AF: 0.233 AC: 9682 AN: 41504

American (AMR) AF: 0.226 AC: 3454 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1344 AN: 3468

East Asian (EAS) AF: 0.136 AC: 706 AN: 5182

South Asian (SAS) AF: 0.197 AC: 952 AN: 4828

European-Finnish (FIN) AF: 0.302 AC: 3197 AN: 10582

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22037 AN: 67968

Other (OTH) AF: 0.290 AC: 613 AN: 2114

Alfa AF: 0.216 Hom.: 693

Bravo AF: 0.274

Asia WGS AF: 0.165 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.65
DANN	Benign	0.49
PhyloP100		-1.2

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

Other links and lift over

dbSNP: rs1093994; hg19: chr17-73614794;