rs3917848

Variant names:

• chr1-169590553-A-C
• rs3917848
• NM_003005.4:c.2439-351T>G

Variant summary

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

The NM_003005.4(SELP):​c.2439-351T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 145,580 control chromosomes in the GnomAD database, including 1,089 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 0.11 (1089 hom., cov: 32)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 7 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELP	NM_003005.4	c.2439-351T>G		intron_variant	Intron 15 of 16	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.2439-351T>G		intron_variant	Intron 15 of 16	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16051 AN: 145466 Hom.: 1080 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.00863

Gnomad SAS AF: 0.0457

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0890

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.111 AC: 16087 AN: 145580 Hom.: 1089 Cov.: 32 AF XY: 0.108 AC XY: 7634 AN XY: 70748

African (AFR) AF: 0.194 AC: 7482 AN: 38550

American (AMR) AF: 0.0861 AC: 1235 AN: 14344

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 396 AN: 3444

East Asian (EAS) AF: 0.00865 AC: 40 AN: 4626

South Asian (SAS) AF: 0.0457 AC: 207 AN: 4532

European-Finnish (FIN) AF: 0.0403 AC: 399 AN: 9894

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.0890 AC: 5958 AN: 66976

Other (OTH) AF: 0.111 AC: 223 AN: 2012

Alfa AF: 0.0970 Hom.: 995

Bravo AF: 0.113

Asia WGS AF: 0.0520 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.2
DANN	Benign	0.55
PhyloP100		0.043
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: rs3917848; hg19: chr1-169559791;