1-169613079-C-T

Variant names:

• chr1-169613079-C-T
• rs6125
• NM_003005.4:c.625G>A

Variant summary

Our verdict is Benign. The variant received -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. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 28 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003005.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELP	NM_003005.4	MANE Select	c.625G>A	p.Val209Met	missense	Exon 5 of 17	NP_002996.2	P16109

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELP	ENST00000263686.11	TSL:1 MANE Select	c.625G>A	p.Val209Met	missense	Exon 5 of 17	ENSP00000263686.5	P16109
	SELP	ENST00000426706.6	TSL:1	c.622G>A	p.Val208Met	missense	Exon 4 of 15	ENSP00000391694.2	Q5R349
	SELP	ENST00000909597.1		c.625G>A	p.Val209Met	missense	Exon 5 of 17	ENSP00000579656.1

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

GnomAD2 exomes AF: 0.0563 AC: 14070 AN: 249926 AF XY: 0.0603

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 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

African (AFR) AF: 0.0388 AC: 1298 AN: 33434

American (AMR) AF: 0.0256 AC: 1140 AN: 44468

Ashkenazi Jewish (ASJ) AF: 0.0402 AC: 1049 AN: 26066

East Asian (EAS) AF: 0.00431 AC: 171 AN: 39638

South Asian (SAS) AF: 0.109 AC: 9378 AN: 86002

European-Finnish (FIN) AF: 0.0770 AC: 4106 AN: 53318

Middle Eastern (MID) AF: 0.0442 AC: 250 AN: 5656

European-Non Finnish (NFE) AF: 0.0542 AC: 60255 AN: 1110746

Other (OTH) AF: 0.0512 AC: 3085 AN: 60292

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

African (AFR) AF: 0.0416 AC: 1729 AN: 41540

American (AMR) AF: 0.0434 AC: 663 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0406 AC: 141 AN: 3470

East Asian (EAS) AF: 0.00830 AC: 43 AN: 5182

South Asian (SAS) AF: 0.111 AC: 536 AN: 4818

European-Finnish (FIN) AF: 0.0702 AC: 744 AN: 10598

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0566 AC: 3851 AN: 68004

Other (OTH) AF: 0.0525 AC: 111 AN: 2114

Alfa AF: 0.0543 Hom.: 1138

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 v4.9

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
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.021
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.080
Sift	Benign	0.14	T
Sift4G	Benign	0.064	T
Vest4		0.037
MPC		0.063
ClinPred		0.0016	T
GERP RS		0.33
gMVP		0.48
Mutation Taster		=100/0	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: rs6125; hg19: chr1-169582317; COSMIC: COSV55250501;