1-169617092-C-T

Variant names:

• chr1-169617092-C-T
• rs6129
• NM_003005.4:c.417G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000263686.11(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 ENST00000263686.11 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.79
• Publications: 5 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.005).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000263686.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELP	NM_003005.4	MANE Select	c.417G>A	p.Pro139Pro	synonymous	Exon 3 of 17	NP_002996.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELP	ENST00000263686.11	TSL:1 MANE Select	c.417G>A	p.Pro139Pro	synonymous	Exon 3 of 17	ENSP00000263686.5
	SELP	ENST00000426706.6	TSL:1	c.414G>A	p.Pro138Pro	synonymous	Exon 2 of 15	ENSP00000391694.2
	SELP	ENST00000367786.6	TSL:5	c.417G>A	p.Pro139Pro	synonymous	Exon 3 of 16	ENSP00000356760.1

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

GnomAD2 exomes AF: 0.0101 AC: 2548 AN: 251274 AF XY: 0.00877

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 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

African (AFR) AF: 0.0702 AC: 2349 AN: 33480

American (AMR) AF: 0.00850 AC: 380 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00781 AC: 204 AN: 26132

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.00128 AC: 110 AN: 86256

European-Finnish (FIN) AF: 0.00339 AC: 181 AN: 53418

Middle Eastern (MID) AF: 0.0181 AC: 104 AN: 5756

European-Non Finnish (NFE) AF: 0.00837 AC: 9312 AN: 1111982

Other (OTH) AF: 0.0123 AC: 743 AN: 60394

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

African (AFR) AF: 0.0641 AC: 2655 AN: 41416

American (AMR) AF: 0.00964 AC: 147 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3470

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5158

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4782

European-Finnish (FIN) AF: 0.00369 AC: 39 AN: 10568

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00742 AC: 504 AN: 67940

Other (OTH) AF: 0.0256 AC: 54 AN: 2108

Alfa AF: 0.0172 Hom.: 31

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.8
DANN	Benign	0.41
PhyloP100		-5.8
Mutation Taster		=98/2	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: rs6129; hg19: chr1-169586330;