1-169594892-T-G

Variant summary

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

The NM_003005.4(SELP):c.2102-15A>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,602,256 control chromosomes in the GnomAD database, including 45,010 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 0.30 (9168 hom., cov: 33)
  • Exomes 𝑓: 0.21 (35842 hom.)
• Consequence: SELP NM_003005.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELP	NM_003005.4	c.2102-15A>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000263686.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELP	ENST00000263686.11	c.2102-15A>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003005.4	P1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45133 AN: 152012 Hom.: 9153 Cov.: 33

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.00829

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.280

GnomAD3 exomes AF: 0.190 AC: 47024 AN: 247080 Hom.: 6558 AF XY: 0.182 AC XY: 24312 AN XY: 133468

Gnomad AFR exome AF: 0.589

Gnomad AMR exome AF: 0.145

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.00855

Gnomad SAS exome AF: 0.0780

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.207 AC: 300204 AN: 1450124 Hom.: 35842 Cov.: 30 AF XY: 0.202 AC XY: 145672 AN XY: 720114

Gnomad4 AFR exome AF: 0.591

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.0118

Gnomad4 SAS exome AF: 0.0781

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.297 AC: 45189 AN: 152132 Hom.: 9168 Cov.: 33 AF XY: 0.286 AC XY: 21271 AN XY: 74376

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.00830

Gnomad4 SAS AF: 0.0746

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.279

Alfa AF: 0.245 Hom.: 2332

Bravo AF: 0.317

Asia WGS AF: 0.0930 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	6.7
Dann	Benign	0.70

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: rs1569471; hg19: chr1-169564130; COSMIC: COSV55248035; COSMIC: COSV55248035;