rs6125

Positions:

• chr1-169613079-C-T

Variant summary

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

The NM_003005.4(SELP):​c.625G>A​(p.Val209Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.055 in 1,611,844 control chromosomes in the GnomAD database, including 2,919 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.052 (253 hom., cov: 32)
  • Exomes 𝑓: 0.055 (2666 hom.)
• Consequence: SELP NM_003005.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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 (MetaRNN=0.00212124).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELP	NM_003005.4	c.625G>A	p.Val209Met	missense_variant	5/17	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.625G>A	p.Val209Met	missense_variant	5/17	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.0520 AC: 7910 AN: 152106 Hom.: 252 Cov.: 32

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.00828

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0702

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.0531

GnomAD3 exomes AF: 0.0563 AC: 14070 AN: 249926 Hom.: 556 AF XY: 0.0603 AC XY: 8152 AN XY: 135080

Gnomad AFR exome AF: 0.0417

Gnomad AMR exome AF: 0.0231

Gnomad ASJ exome AF: 0.0377

Gnomad EAS exome AF: 0.00894

Gnomad SAS exome AF: 0.111

Gnomad FIN exome AF: 0.0775

Gnomad NFE exome AF: 0.0589

Gnomad OTH exome AF: 0.0576

GnomAD4 exome AF: 0.0553 AC: 80732 AN: 1459620 Hom.: 2666 Cov.: 31 AF XY: 0.0574 AC XY: 41677 AN XY: 725952

Gnomad4 AFR exome AF: 0.0388

Gnomad4 AMR exome AF: 0.0256

Gnomad4 ASJ exome AF: 0.0402

Gnomad4 EAS exome AF: 0.00431

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.0770

Gnomad4 NFE exome AF: 0.0542

Gnomad4 OTH exome AF: 0.0512

GnomAD4 genome AF: 0.0519 AC: 7904 AN: 152224 Hom.: 253 Cov.: 32 AF XY: 0.0517 AC XY: 3845 AN XY: 74438

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.0434

Gnomad4 ASJ AF: 0.0406

Gnomad4 EAS AF: 0.00830

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0702

Gnomad4 NFE AF: 0.0566

Gnomad4 OTH AF: 0.0525

Alfa AF: 0.0536 Hom.: 600

Bravo AF: 0.0474

TwinsUK AF: 0.0537 AC: 199

ALSPAC AF: 0.0542 AC: 209

ESP6500AA AF: 0.0406 AC: 179

ESP6500EA AF: 0.0542 AC: 466

ExAC AF: 0.0593 AC: 7198

Asia WGS AF: 0.0530 AC: 187 AN: 3478

EpiCase AF: 0.0538

EpiControl AF: 0.0526

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T;.;T;T;T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.68	T;T;T;T;T;T
MetaRNN	Benign	0.0021	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.55	N;N;N;.;N;N
REVEL	Benign	0.080
Sift	Benign	0.14	T;T;D;.;D;D
Sift4G	Benign	0.064	T;T;T;T;D;.
Vest4		0.037, 0.064, 0.061, 0.034
MPC		0.063
ClinPred		0.0016	T
GERP RS		0.33
gMVP		0.48

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: rs6125; hg19: chr1-169582317; COSMIC: COSV55250501;