rs3917681

Positions:

• chr1-169622465-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.4-3246T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 152,296 control chromosomes in the GnomAD database, including 918 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 0.097 (918 hom., cov: 33)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELP	NM_003005.4	c.4-3246T>C		intron_variant		ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.4-3246T>C		intron_variant		1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 14836 AN: 152178 Hom.: 916 Cov.: 33

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.0974 AC: 14839 AN: 152296 Hom.: 918 Cov.: 33 AF XY: 0.0975 AC XY: 7260 AN XY: 74476

Gnomad4 AFR AF: 0.0319

Gnomad4 AMR AF: 0.0729

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.115

Alfa AF: 0.106 Hom.: 147

Bravo AF: 0.0926

Asia WGS AF: 0.161 AC: 560 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.89

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: rs3917681; hg19: chr1-169591703;