Variant 1-169596108-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.23 ( 7146 hom., cov: 32)

Exomes 𝑓: 0.12 ( 15055 hom. )

Consequence

SELP
NM_003005.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.576

Variant links:

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]

SELP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SELP	NM_003005.4 linkuse as main transcript	c.1918G>T	p.Val640Leu	missense_variant	12/17	ENST00000263686.11	NP_002996.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELP	ENST00000263686.11 linkuse as main transcript	c.1918G>T	p.Val640Leu	missense_variant	12/17	1	NM_003005.4	ENSP00000263686	P1

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34726

AN:

151890

Hom.:

7132

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.119

AC:

29847

AN:

250988

Hom.:

3851

AF XY:

0.108

AC XY:

14689

AN XY:

135620

show subpopulations

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 SAS exome

AF:

0.0266

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.:

AF XY:

0.115

AC XY:

83370

AN XY:

726954

show subpopulations

Gnomad4 AFR exome

AF:

0.572

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.0946

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0259

Gnomad4 FIN exome

AF:

0.0818

Gnomad4 NFE exome

AF:

0.119

Gnomad4 OTH exome

AF:

0.138

GnomAD4 genome

AF:

0.229

AC:

34786

AN:

152008

Hom.:

7146

Cov.:

AF XY:

0.221

AC XY:

16398

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.556

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.0856

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0259

Gnomad4 FIN

AF:

0.0770

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.201

Alfa

AF:

0.130

Hom.:

4705

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

LINK: link

Submissions by phenotype

SELP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 06, 2019

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

BayesDel_noAF

Benign

-0.66

CADD

Benign

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

LIST_S2

Benign

0.64

T;T;T;T;T

MetaRNN

Benign

0.000065

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.34

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

GERP RS

3.2

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over