rs2244526

Positions:

• chr1-169617708-T-C

Variant summary

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

The NM_003005.4(SELP):​c.95-294A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,170 control chromosomes in the GnomAD database, including 1,358 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 0.13 (1358 hom., cov: 32)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELP	NM_003005.4	c.95-294A>G		intron_variant		ENST00000263686.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELP	ENST00000263686.11	c.95-294A>G		intron_variant		1	NM_003005.4	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19344 AN: 152052 Hom.: 1352 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0955

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.127 AC: 19375 AN: 152170 Hom.: 1358 Cov.: 32 AF XY: 0.130 AC XY: 9697 AN XY: 74406

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0955

Gnomad4 OTH AF: 0.110

Alfa AF: 0.100 Hom.: 783

Bravo AF: 0.132

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.69

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: rs2244526; hg19: chr1-169586946;