rs3917734

Positions:

• chr1-169611225-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.1147+267C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,098 control chromosomes in the GnomAD database, including 3,458 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 0.19 (3458 hom., cov: 32)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELP	NM_003005.4	c.1147+267C>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.1147+267C>T		intron_variant		1	NM_003005.4	ENSP00000263686	P1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28210 AN: 151980 Hom.: 3458 Cov.: 32

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.185 AC: 28200 AN: 152098 Hom.: 3458 Cov.: 32 AF XY: 0.180 AC XY: 13350 AN XY: 74370

Gnomad4 AFR AF: 0.0516

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.207

Alfa AF: 0.208 Hom.: 551

Bravo AF: 0.177

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.15
DANN	Benign	0.68

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: rs3917734; hg19: chr1-169580463;