NM_003005.4:c.4-4530T>G

Variant names:

• chr1-169623749-A-C
• rs2236867
• NM_003005.4:c.4-4530T>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.4-4530T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,512 control chromosomes in the GnomAD database, including 24,928 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 0.57 (24928 hom., cov: 31)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELP	NM_003005.4	c.4-4530T>G		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.4-4530T>G		intron_variant	Intron 1 of 16	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86081 AN: 151394 Hom.: 24891 Cov.: 31

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.569 AC: 86168 AN: 151512 Hom.: 24928 Cov.: 31 AF XY: 0.564 AC XY: 41734 AN XY: 74044

African (AFR) AF: 0.650 AC: 26797 AN: 41240

American (AMR) AF: 0.487 AC: 7437 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2024 AN: 3462

East Asian (EAS) AF: 0.351 AC: 1809 AN: 5154

South Asian (SAS) AF: 0.506 AC: 2436 AN: 4812

European-Finnish (FIN) AF: 0.525 AC: 5503 AN: 10472

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38262 AN: 67812

Other (OTH) AF: 0.576 AC: 1210 AN: 2102

Alfa AF: 0.565 Hom.: 3418

Bravo AF: 0.570

Asia WGS AF: 0.424 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.69
PhyloP100		-0.64
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: rs2236867; hg19: chr1-169592987;