1-169596108-C-A

Variant names:

• chr1-169596108-C-A
• rs6133
• NM_003005.4:c.1918G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_003005.4(SELP):​c.1918G>T​(p.Val640Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,262 control chromosomes in the GnomAD database, including 22,201 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (7146 hom., cov: 32)
  • Exomes 𝑓: 0.12 (15055 hom.)
• Consequence: SELP NM_003005.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.576

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 (MetaRNN=6.503283E-5).
• BP6: Variant 1-169596108-C-A is Benign according to our data. Variant chr1-169596108-C-A is described in ClinVar as [Benign]. Clinvar id is 3056507.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELP	NM_003005.4	c.1918G>T	p.Val640Leu	missense_variant	Exon 12 of 17	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11	c.1918G>T	p.Val640Leu	missense_variant	Exon 12 of 17	1	NM_003005.4	ENSP00000263686.5

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34726 AN: 151890 Hom.: 7132 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0856

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0770

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.201

GnomAD2 exomes AF: 0.119 AC: 29847 AN: 250988 AF XY: 0.108

Gnomad AFR exome AF: 0.570

Gnomad AMR exome AF: 0.0980

Gnomad ASJ exome AF: 0.0953

Gnomad EAS exome AF: 0.000653

Gnomad FIN exome AF: 0.0801

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.119 AC: 174141 AN: 1461254 Hom.: 15055 Cov.: 32 AF XY: 0.115 AC XY: 83370 AN XY: 726954

Gnomad4 AFR exome AF: 0.572 AC: 19118 AN: 33434

Gnomad4 AMR exome AF: 0.104 AC: 4635 AN: 44704

Gnomad4 ASJ exome AF: 0.0946 AC: 2470 AN: 26110

Gnomad4 EAS exome AF: 0.000378 AC: 15 AN: 39698

Gnomad4 SAS exome AF: 0.0259 AC: 2231 AN: 86246

Gnomad4 FIN exome AF: 0.0818 AC: 4369 AN: 53416

Gnomad4 NFE exome AF: 0.119 AC: 132240 AN: 1111512

Gnomad4 Remaining exome AF: 0.138 AC: 8315 AN: 60374

GnomAD4 genome AF: 0.229 AC: 34786 AN: 152008 Hom.: 7146 Cov.: 32 AF XY: 0.221 AC XY: 16398 AN XY: 74316

Gnomad4 AFR AF: 0.556 AC: 0.556087 AN: 0.556087

Gnomad4 AMR AF: 0.143 AC: 0.143054 AN: 0.143054

Gnomad4 ASJ AF: 0.0856 AC: 0.0856401 AN: 0.0856401

Gnomad4 EAS AF: 0.000965 AC: 0.000964506 AN: 0.000964506

Gnomad4 SAS AF: 0.0259 AC: 0.0259336 AN: 0.0259336

Gnomad4 FIN AF: 0.0770 AC: 0.0770102 AN: 0.0770102

Gnomad4 NFE AF: 0.116 AC: 0.115832 AN: 0.115832

Gnomad4 OTH AF: 0.201 AC: 0.201422 AN: 0.201422

Alfa AF: 0.139 Hom.: 8319

Bravo AF: 0.252

TwinsUK AF: 0.125 AC: 463

ALSPAC AF: 0.120 AC: 461

ESP6500AA AF: 0.550 AC: 2425

ESP6500EA AF: 0.117 AC: 1003

ExAC AF: 0.127 AC: 15441

Asia WGS AF: 0.0530 AC: 188 AN: 3478

EpiCase AF: 0.117

EpiControl AF: 0.121

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SELP-related disorder Benign:1

Nov 06, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.013	T;.;T;T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.81
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.64	T;T;T;T;T
MetaRNN	Benign	0.000065	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.89	N;N;N;.;N
REVEL	Benign	0.0080
Sift	Benign	0.15	T;T;T;.;T
Sift4G	Benign	0.25	T;T;T;T;T
Vest4		0.23, 0.078, 0.22, 0.074
MutPred		0.37		.;Gain of glycosylation at P638 (P = 0.0801);.;.;.;
MPC		0.061
ClinPred		0.0016	T
GERP RS		3.2
gMVP		0.25
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs6133; hg19: chr1-169565346; COSMIC: COSV55250110; COSMIC: COSV55250110;