dbSNP rs3917422: SELE:p.Gln257Pro (chr1-169729619-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000450.2(SELE):c.770A>C(p.Gln257Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,614,152 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0065 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 12 hom. )

Consequence

SELE
NM_000450.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.328

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:

C1orf112 (HGNC:25565): (FIGNL1 interacting regulator of recombination and mitosis)

C1orf112 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039951503).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00655 (997/152306) while in subpopulation AFR AF= 0.0228 (947/41560). AF 95% confidence interval is 0.0216. There are 9 homozygotes in gnomad4. There are 490 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELE	NM_000450.2 link	c.770A>C	p.Gln257Pro	missense_variant	Exon 6 of 14	ENST00000333360.12	NP_000441.2	P16581

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELE	ENST00000333360.12 link	c.770A>C	p.Gln257Pro	missense_variant	Exon 6 of 14	1	NM_000450.2	ENSP00000331736.7		P16581

Frequencies

GnomAD3 genomes

AF:

0.00655

AC:

997

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00186

AC:

466

AN:

251140

Hom.:

AF XY:

0.00149

AC XY:

202

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.0243

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000725

AC:

1060

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000655

AC XY:

476

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.0230

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000110

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.00655

AC:

997

AN:

152306

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

490

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00250

Hom.:

Bravo

AF:

0.00768

ESP6500AA

AF:

0.0204

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00220

AC:

267

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.0010

DANN

Benign

0.38

DEOGEN2

Benign

0.018

.;T;T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.22

T;T;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.40

.;.;.;N;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.7

N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.13

T;T;T;T;T

Sift4G

Benign

0.22

T;T;T;T;T

Polyphen

0.0

.;.;.;B;.

Vest4

0.12

MVP

0.32

MPC

0.066

ClinPred

0.018

GERP RS

-11

gMVP

0.82

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