rs3917683

Variant names:

• chr1-169622135-T-C
• rs3917683
• NM_003005.4:c.4-2916A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003005.4(SELP):​c.4-2916A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,142 control chromosomes in the GnomAD database, including 25,066 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 0.57 (25066 hom., cov: 34)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.540
• Publications: 6 publications found

Genes affected

SELP (HGNC:10721): (selectin P) This gene encodes a 140 kDa protein that is stored in the alpha-granules of platelets and Weibel-Palade bodies of endothelial cells. This protein redistributes to the plasma membrane during platelet activation and degranulation and mediates the interaction of activated endothelial cells or platelets with leukocytes. The membrane protein is a calcium-dependent receptor that binds to sialylated forms of Lewis blood group carbohydrate antigens on neutrophils and monocytes. Alternative splice variants may occur but are not well documented. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELP	NM_003005.4	c.4-2916A>G		intron_variant	Intron 1 of 16	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.4-2916A>G		intron_variant	Intron 1 of 16	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86370 AN: 152022 Hom.: 25029 Cov.: 34

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.568 AC: 86458 AN: 152142 Hom.: 25066 Cov.: 34 AF XY: 0.563 AC XY: 41882 AN XY: 74366

African (AFR) AF: 0.650 AC: 26961 AN: 41494

American (AMR) AF: 0.481 AC: 7359 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2028 AN: 3472

East Asian (EAS) AF: 0.354 AC: 1835 AN: 5186

South Asian (SAS) AF: 0.499 AC: 2406 AN: 4826

European-Finnish (FIN) AF: 0.529 AC: 5592 AN: 10564

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38372 AN: 67990

Other (OTH) AF: 0.572 AC: 1209 AN: 2114

Alfa AF: 0.565 Hom.: 12582

Bravo AF: 0.568

Asia WGS AF: 0.417 AC: 1450 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.8
DANN	Benign	0.50
PhyloP100		-0.54
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

Other links and lift over

dbSNP: rs3917683; hg19: chr1-169591373;