1-169621556-A-G

Position:

• chr1-169621556-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003005.4(SELP):​c.4-2337T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 151,684 control chromosomes in the GnomAD database, including 44,584 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 0.76 (44584 hom., cov: 29)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELP	NM_003005.4	c.4-2337T>C		intron_variant		ENST00000263686.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELP	ENST00000263686.11	c.4-2337T>C		intron_variant		1	NM_003005.4	P1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115626 AN: 151566 Hom.: 44540 Cov.: 29

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.834

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.763 AC: 115715 AN: 151684 Hom.: 44584 Cov.: 29 AF XY: 0.755 AC XY: 55962 AN XY: 74084

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.761

Alfa AF: 0.747 Hom.: 45209

Bravo AF: 0.768

Asia WGS AF: 0.714 AC: 2486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.056
DANN	Benign	0.36

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: rs3917691; hg19: chr1-169590794;