1-169729301-G-T

Position:

chr1-169729301-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000450.2(SELE):c.975C>A(p.Phe325Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00394 in 1,614,124 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 32 hom. )

Consequence

SELE
NM_000450.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.100

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0082035065).

BS2

High Homozygotes in GnomAdExome4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELE	NM_000450.2 linkuse as main transcript	c.975C>A	p.Phe325Leu	missense_variant	7/14	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.975C>A	p.Phe325Leu	missense_variant	7/14	1	NM_000450.2	ENSP00000331736.7		P16581

Frequencies

GnomAD3 genomes

AF:

0.00323

AC:

492

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000699

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00485

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00352

AC:

884

AN:

250902

Hom.:

AF XY:

0.00365

AC XY:

495

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00286

Gnomad ASJ exome

AF:

0.00756

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00516

Gnomad FIN exome

AF:

0.00162

Gnomad NFE exome

AF:

0.00423

Gnomad OTH exome

AF:

0.00474

GnomAD4 exome

AF:

0.00402

AC:

5876

AN:

1461796

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

2876

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.00754

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00526

Gnomad4 FIN exome

AF:

0.00154

Gnomad4 NFE exome

AF:

0.00423

Gnomad4 OTH exome

AF:

0.00422

GnomAD4 genome

AF:

0.00322

AC:

491

AN:

152328

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

218

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000697

Gnomad4 AMR

AF:

0.00431

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00485

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00433

Hom.:

Bravo

AF:

0.00322

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00488

AC:

ExAC

AF:

0.00333

AC:

404

Asia WGS

AF:

0.00173

AC:

AN:

3476

EpiCase

AF:

0.00605

EpiControl

AF:

0.00510

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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_000450.2 exon 7 p.Phe325Leu (c.975C>A): This variant has not been reported in the literature and is present in 0.7% (77/10346) of Ashkenazi Jewish alleles, including 1 homozygote, in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/1-169698442-G-T). This variant amino acid Leucine (Leu) is present in several species, including multiple mammals, and it is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. 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

Pathogenic

0.68

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.95

DANN

Benign

0.86

DEOGEN2

Benign

0.060

.;T;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.67

T;T;T;T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.0082

T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.4

.;.;.;L;.

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.4

D;D;D;D;D

REVEL

Benign

0.20

Sift

Benign

0.10

T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.10

.;.;.;B;.

Vest4

0.14

MutPred

0.64

.;Gain of ubiquitination at K328 (P = 0.0843);Gain of ubiquitination at K328 (P = 0.0843);Gain of ubiquitination at K328 (P = 0.0843);Gain of ubiquitination at K328 (P = 0.0843);

MVP

0.71

MPC

0.072

ClinPred

0.027

GERP RS

-4.1

gMVP

0.83

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