rs17522707

Positions:

• chr1-169593824-G-A

Variant summary

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

The NM_003005.4(SELP):​c.2288-100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0878 in 1,163,380 control chromosomes in the GnomAD database, including 4,845 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 0.067 (447 hom., cov: 32)
  • Exomes 𝑓: 0.091 (4398 hom.)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.986

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.099 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELP	NM_003005.4	c.2288-100C>T		intron_variant		ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.2288-100C>T		intron_variant		1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.0670 AC: 10190 AN: 152068 Hom.: 446 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0634

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00731

Gnomad SAS AF: 0.0403

Gnomad FIN AF: 0.0595

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0779

GnomAD4 exome AF: 0.0910 AC: 91972 AN: 1011194 Hom.: 4398 AF XY: 0.0906 AC XY: 46184 AN XY: 509644

Gnomad4 AFR exome AF: 0.0175

Gnomad4 AMR exome AF: 0.0549

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.0121

Gnomad4 SAS exome AF: 0.0447

Gnomad4 FIN exome AF: 0.0709

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.0827

GnomAD4 genome AF: 0.0669 AC: 10186 AN: 152186 Hom.: 447 Cov.: 32 AF XY: 0.0642 AC XY: 4778 AN XY: 74392

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.0633

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.00733

Gnomad4 SAS AF: 0.0405

Gnomad4 FIN AF: 0.0595

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0762

Alfa AF: 0.0840 Hom.: 107

Bravo AF: 0.0644

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.32

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: rs17522707; hg19: chr1-169563062; COSMIC: COSV55260458; COSMIC: COSV55260458;