rs2076074

Variant names:

• chr1-169609348-G-A
• rs2076074
• NM_003005.4:c.1333+156C>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.1333+156C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,058 control chromosomes in the GnomAD database, including 4,365 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 0.22 (4365 hom., cov: 32)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.737
• Publications: 17 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELP	NM_003005.4	c.1333+156C>T		intron_variant	Intron 8 of 16	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.1333+156C>T		intron_variant	Intron 8 of 16	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33112 AN: 151940 Hom.: 4359 Cov.: 32

Gnomad AFR AF: 0.0914

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.218 AC: 33126 AN: 152058 Hom.: 4365 Cov.: 32 AF XY: 0.229 AC XY: 16986 AN XY: 74322

African (AFR) AF: 0.0911 AC: 3776 AN: 41454

American (AMR) AF: 0.346 AC: 5294 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 786 AN: 3470

East Asian (EAS) AF: 0.314 AC: 1618 AN: 5158

South Asian (SAS) AF: 0.303 AC: 1462 AN: 4822

European-Finnish (FIN) AF: 0.391 AC: 4127 AN: 10554

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15475 AN: 67996

Other (OTH) AF: 0.218 AC: 461 AN: 2114

Alfa AF: 0.226 Hom.: 9025

Bravo AF: 0.211

Asia WGS AF: 0.296 AC: 1027 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.11
DANN	Benign	0.45
PhyloP100		-0.74
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: rs2076074; hg19: chr1-169578586;