rs3917862

Positions:

• chr1-169623875-A-G

Variant summary

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

The NM_003005.4(SELP):​c.4-4656T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 152,290 control chromosomes in the GnomAD database, including 174 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 0.039 (174 hom., cov: 32)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELP	NM_003005.4	c.4-4656T>C		intron_variant		ENST00000263686.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELP	ENST00000263686.11	c.4-4656T>C		intron_variant		1	NM_003005.4	P1

Frequencies

GnomAD3 genomes AF: 0.0392 AC: 5960 AN: 152172 Hom.: 174 Cov.: 32

Gnomad AFR AF: 0.00941

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0267

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0278

Gnomad FIN AF: 0.0390

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0616

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0391 AC: 5959 AN: 152290 Hom.: 174 Cov.: 32 AF XY: 0.0376 AC XY: 2802 AN XY: 74466

Gnomad4 AFR AF: 0.00938

Gnomad4 AMR AF: 0.0267

Gnomad4 ASJ AF: 0.0680

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0282

Gnomad4 FIN AF: 0.0390

Gnomad4 NFE AF: 0.0617

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0556 Hom.: 114

Bravo AF: 0.0379

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.17
DANN	Benign	0.34

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: rs3917862; hg19: chr1-169593113;