rs3917657

Variant names:

• chr1-169629504-G-A
• rs3917657
• NM_003005.4:c.3+568C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003005.4(SELP):​c.3+568C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 152,218 control chromosomes in the GnomAD database, including 915 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 (915 hom., cov: 33)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• 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 rank	MANE	Protein	UniProt
SELP	NM_003005.4	c.3+568C>T		intron_variant	Intron 1 of 16	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.3+568C>T		intron_variant	Intron 1 of 16	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14735 AN: 152100 Hom.: 918 Cov.: 33

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.0732

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.0967 AC: 14724 AN: 152218 Hom.: 915 Cov.: 33 AF XY: 0.0965 AC XY: 7178 AN XY: 74412

African (AFR) AF: 0.0321 AC: 1332 AN: 41542

American (AMR) AF: 0.0731 AC: 1118 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3472

East Asian (EAS) AF: 0.202 AC: 1046 AN: 5170

South Asian (SAS) AF: 0.106 AC: 513 AN: 4822

European-Finnish (FIN) AF: 0.125 AC: 1320 AN: 10594

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8390 AN: 68002

Other (OTH) AF: 0.110 AC: 233 AN: 2116

Alfa AF: 0.103 Hom.: 144

Bravo AF: 0.0923

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.3
DANN	Benign	0.71
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3917657; hg19: chr1-169598742;