Variant 1-169726729-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000450.2(SELE):c.1723C>T(p.Leu575Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 1,613,330 control chromosomes in the GnomAD database, including 1,727 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.035 ( 122 hom., cov: 32)

Exomes 𝑓: 0.043 ( 1605 hom. )

Consequence

SELE
NM_000450.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002411604).

BP6

Variant 1-169726729-G-A is Benign according to our data. Variant chr1-169726729-G-A is described in ClinVar as [Benign]. Clinvar id is 1684530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0869 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.1723C>T	p.Leu575Phe	missense_variant	11/14	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.1723C>T	p.Leu575Phe	missense_variant	11/14	1	NM_000450.2	ENSP00000331736	P1

Frequencies

GnomAD3 genomes

AF:

0.0346

AC:

5269

AN:

152150

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0323

Gnomad ASJ

AF:

0.0783

Gnomad EAS

AF:

0.0469

Gnomad SAS

AF:

0.0936

Gnomad FIN

AF:

0.0352

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0391

Gnomad OTH

AF:

0.0497

GnomAD3 exomes

AF:

0.0451

AC:

11311

AN:

250758

Hom.:

348

AF XY:

0.0479

AC XY:

6492

AN XY:

135504

show subpopulations

Gnomad AFR exome

AF:

0.0146

Gnomad AMR exome

AF:

0.0306

Gnomad ASJ exome

AF:

0.0688

Gnomad EAS exome

AF:

0.0518

Gnomad SAS exome

AF:

0.0953

Gnomad FIN exome

AF:

0.0353

Gnomad NFE exome

AF:

0.0386

Gnomad OTH exome

AF:

0.0544

GnomAD4 exome

AF:

0.0431

AC:

63032

AN:

1461062

Hom.:

1605

Cov.:

AF XY:

0.0449

AC XY:

32652

AN XY:

726852

show subpopulations

Gnomad4 AFR exome

AF:

0.0151

Gnomad4 AMR exome

AF:

0.0314

Gnomad4 ASJ exome

AF:

0.0718

Gnomad4 EAS exome

AF:

0.0507

Gnomad4 SAS exome

AF:

0.0915

Gnomad4 FIN exome

AF:

0.0372

Gnomad4 NFE exome

AF:

0.0394

Gnomad4 OTH exome

AF:

0.0512

GnomAD4 genome

AF:

0.0346

AC:

5266

AN:

152268

Hom.:

122

Cov.:

AF XY:

0.0355

AC XY:

2641

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0152

Gnomad4 AMR

AF:

0.0322

Gnomad4 ASJ

AF:

0.0783

Gnomad4 EAS

AF:

0.0470

Gnomad4 SAS

AF:

0.0941

Gnomad4 FIN

AF:

0.0352

Gnomad4 NFE

AF:

0.0390

Gnomad4 OTH

AF:

0.0497

Alfa

AF:

0.0413

Hom.:

316

Bravo

AF:

0.0334

TwinsUK

AF:

0.0361

AC:

134

ALSPAC

AF:

0.0451

AC:

174

ESP6500AA

AF:

0.0172

AC:

ESP6500EA

AF:

0.0428

AC:

368

ExAC

AF:

0.0456

AC:

5532

Asia WGS

AF:

0.0870

AC:

301

AN:

3476

EpiCase

AF:

0.0416

EpiControl

AF:

0.0423

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Coronary artery disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Rasad Genetic Department, Rasad Pathobiology and Genetic Laboratory

May 12, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

.;T;T;T;.

Eigen

Benign

-0.064

Eigen_PC

Benign

-0.018

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.74

T;T;T;T;T

MetaRNN

Benign

0.0024

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

.;.;.;M;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.63

N;N;N;N;N

REVEL

Benign

0.074

Sift

Benign

0.18

T;T;T;D;T

Sift4G

Uncertain

0.030

D;D;D;D;D

Polyphen

0.39

.;.;.;B;.

Vest4

0.46

MPC

0.10

ClinPred

0.014

GERP RS

4.6

gMVP

0.45

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over