1-169617092-C-T

Position:

• chr1-169617092-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003005.4(SELP):​c.417G>A​(p.Pro139Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,613,744 control chromosomes in the GnomAD database, including 225 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 0.023 (80 hom., cov: 32)
  • Exomes 𝑓: 0.0092 (145 hom.)
• Consequence: SELP NM_003005.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.79

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-5.79 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELP	NM_003005.4	c.417G>A	p.Pro139Pro	synonymous_variant	3/17	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.417G>A	p.Pro139Pro	synonymous_variant	3/17	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3432 AN: 151784 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.0640

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00965

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.00369

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00742

Gnomad OTH AF: 0.0259

GnomAD3 exomes AF: 0.0101 AC: 2548 AN: 251274 Hom.: 41 AF XY: 0.00877 AC XY: 1191 AN XY: 135786

Gnomad AFR exome AF: 0.0679

Gnomad AMR exome AF: 0.00760

Gnomad ASJ exome AF: 0.00744

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00105

Gnomad FIN exome AF: 0.00310

Gnomad NFE exome AF: 0.00825

Gnomad OTH exome AF: 0.0113

GnomAD4 exome AF: 0.00916 AC: 13389 AN: 1461842 Hom.: 145 Cov.: 34 AF XY: 0.00863 AC XY: 6277 AN XY: 727228

Gnomad4 AFR exome AF: 0.0702

Gnomad4 AMR exome AF: 0.00850

Gnomad4 ASJ exome AF: 0.00781

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.00128

Gnomad4 FIN exome AF: 0.00339

Gnomad4 NFE exome AF: 0.00837

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.0227 AC: 3442 AN: 151902 Hom.: 80 Cov.: 32 AF XY: 0.0224 AC XY: 1664 AN XY: 74250

Gnomad4 AFR AF: 0.0641

Gnomad4 AMR AF: 0.00964

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.00369

Gnomad4 NFE AF: 0.00742

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0168 Hom.: 30

Bravo AF: 0.0259

Asia WGS AF: 0.00636 AC: 22 AN: 3476

EpiCase AF: 0.00720

EpiControl AF: 0.00788

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.8
DANN	Benign	0.41

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: rs6129; hg19: chr1-169586330;