1-169726804-G-A

Position:

chr1-169726804-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000450.2(SELE):c.1648C>T(p.Pro550Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000241 in 1,608,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SELE
NM_000450.2 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.786

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:):

C1orf112 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.003974259).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELE	NM_000450.2 linkuse as main transcript	c.1648C>T	p.Pro550Ser	missense_variant, splice_region_variant	11/14	ENST00000333360.12	NP_000441.2	P16581

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELE	ENST00000333360.12 linkuse as main transcript	c.1648C>T	p.Pro550Ser	missense_variant, splice_region_variant	11/14	1	NM_000450.2	ENSP00000331736.7		P16581

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00488

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000345

AC:

AN:

249538

Hom.:

AF XY:

0.000245

AC XY:

AN XY:

134746

show subpopulations

Gnomad AFR exome

AF:

0.00521

Gnomad AMR exome

AF:

0.0000291

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:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000122

AC:

177

AN:

1456344

Hom.:

Cov.:

AF XY:

0.0000980

AC XY:

AN XY:

724744

show subpopulations

Gnomad4 AFR exome

AF:

0.00477

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.00139

AC:

211

AN:

152294

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00486

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000202

Hom.:

Bravo

AF:

0.00151

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000486

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000596

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Mar 30, 2021

SELE NM_000450 exon 11 p.Pro550Ser (c.1648C>T): This variant has not been reported in the literature but is present in 0.4% (119/23902) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs3917429). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

.;T;T;T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.76

T;T;T;T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0040

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;.;.;L;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.7

D;D;D;D;D

REVEL

Benign

0.051

Sift

Benign

0.061

T;T;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T

Polyphen

0.84

.;.;.;P;.

Vest4

0.12

MVP

0.51

MPC

0.091

ClinPred

0.058

GERP RS

1.8

gMVP

0.46

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