1-169621926-T-C

Position:

• chr1-169621926-T-C

Variant summary

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

The NM_003005.4(SELP):​c.4-2707A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,122 control chromosomes in the GnomAD database, including 5,102 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 0.21 (5102 hom., cov: 33)
• Consequence: SELP NM_003005.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.375

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELP	NM_003005.4	c.4-2707A>G		intron_variant		ENST00000263686.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELP	ENST00000263686.11	c.4-2707A>G		intron_variant		1	NM_003005.4	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32016 AN: 152004 Hom.: 5077 Cov.: 33

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.211 AC: 32095 AN: 152122 Hom.: 5102 Cov.: 33 AF XY: 0.212 AC XY: 15765 AN XY: 74350

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.175

Alfa AF: 0.124 Hom.: 1528

Bravo AF: 0.225

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.72

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: rs3917686; hg19: chr1-169591164;