Variant chr1-169731919-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000333360.12(SELE):c.445A>C(p.Ser149Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,612,270 control chromosomes in the GnomAD database, including 7,453 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.078 ( 562 hom., cov: 31)

Exomes 𝑓: 0.093 ( 6891 hom. )

Consequence

SELE
ENST00000333360.12 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.34

Variant links:

Genes affected

SELE (HGNC:10718): (selectin E) The protein encoded by this gene is found in cytokine-stimulated endothelial cells and is thought to be responsible for the accumulation of blood leukocytes at sites of inflammation by mediating the adhesion of cells to the vascular lining. It exhibits structural features such as the presence of lectin- and EGF-like domains followed by short consensus repeat (SCR) domains that contain 6 conserved cysteine residues. These proteins are part of the selectin family of cell adhesion molecules. Adhesion molecules participate in the interaction between leukocytes and the endothelium and appear to be involved in the pathogenesis of atherosclerosis. [provided by RefSeq, Jul 2008]

SELE links:

FIRRM (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

FIRRM links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030622482).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELE	NM_000450.2 linkuse as main transcript	c.445A>C	p.Ser149Arg	missense_variant	4/14	ENST00000333360.12	NP_000441.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELE	ENST00000333360.12 linkuse as main transcript	c.445A>C	p.Ser149Arg	missense_variant	4/14	1	NM_000450.2	ENSP00000331736	P1

Frequencies

GnomAD3 genomes

AF:

0.0779

AC:

11854

AN:

152106

Hom.:

562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0389

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.0647

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.0168

Gnomad SAS

AF:

0.0742

Gnomad FIN

AF:

0.0720

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0856

GnomAD3 exomes

AF:

0.0827

AC:

20737

AN:

250828

Hom.:

1060

AF XY:

0.0855

AC XY:

11587

AN XY:

135564

show subpopulations

Gnomad AFR exome

AF:

0.0367

Gnomad AMR exome

AF:

0.0493

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.0137

Gnomad SAS exome

AF:

0.0840

Gnomad FIN exome

AF:

0.0748

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.0984

GnomAD4 exome

AF:

0.0934

AC:

136412

AN:

1460046

Hom.:

6891

Cov.:

AF XY:

0.0940

AC XY:

68287

AN XY:

726384

show subpopulations

Gnomad4 AFR exome

AF:

0.0362

Gnomad4 AMR exome

AF:

0.0514

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.0273

Gnomad4 SAS exome

AF:

0.0810

Gnomad4 FIN exome

AF:

0.0779

Gnomad4 NFE exome

AF:

0.0996

Gnomad4 OTH exome

AF:

0.0953

GnomAD4 genome

AF:

0.0779

AC:

11856

AN:

152224

Hom.:

562

Cov.:

AF XY:

0.0757

AC XY:

5634

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0389

Gnomad4 AMR

AF:

0.0646

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.0168

Gnomad4 SAS

AF:

0.0743

Gnomad4 FIN

AF:

0.0720

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.0838

Alfa

AF:

0.0977

Hom.:

2074

Bravo

AF:

0.0748

TwinsUK

AF:

0.0957

AC:

355

ALSPAC

AF:

0.0999

AC:

385

ESP6500AA

AF:

0.0413

AC:

182

ESP6500EA

AF:

0.106

AC:

909

ExAC

AF:

0.0841

AC:

10215

Asia WGS

AF:

0.0470

AC:

165

AN:

3478

EpiCase

AF:

0.108

EpiControl

AF:

0.105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.45

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

.;D;D;D;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D;D;D;D

MetaRNN

Benign

0.0031

T;T;T;T;T

MetaSVM

Uncertain

0.53

MutationAssessor

Benign

1.6

.;.;.;L;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.7

D;D;D;D;D

REVEL

Uncertain

0.52

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Uncertain

0.015

D;D;D;D;D

Polyphen

1.0

.;.;.;D;.

Vest4

0.70

MutPred

0.24

Loss of glycosylation at S149 (P = 0.0086);Loss of glycosylation at S149 (P = 0.0086);Loss of glycosylation at S149 (P = 0.0086);Loss of glycosylation at S149 (P = 0.0086);Loss of glycosylation at S149 (P = 0.0086);

MPC

0.37

ClinPred

0.011

GERP RS

4.4

gMVP

0.54

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over