NM_000450.2:c.1723C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

47 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SELE	NM_000450.2 link	c.1723C>T	p.Leu575Phe	missense_variant	Exon 11 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.1723C>T	p.Leu575Phe	missense_variant	Exon 11 of 14	1	NM_000450.2	ENSP00000331736.7		P16581

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

GnomAD2 exomes

AF:

0.0451

AC:

11311

AN:

250758

AF XY:

0.0479

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 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

African (AFR)

AF:

0.0151

AC:

505

AN:

33470

American (AMR)

AF:

0.0314

AC:

1402

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0718

AC:

1874

AN:

26116

East Asian (EAS)

AF:

0.0507

AC:

2013

AN:

39676

South Asian (SAS)

AF:

0.0915

AC:

7882

AN:

86154

European-Finnish (FIN)

AF:

0.0372

AC:

1985

AN:

53406

Middle Eastern (MID)

AF:

0.0867

AC:

500

AN:

5764

European-Non Finnish (NFE)

AF:

0.0394

AC:

43783

AN:

1111402

Other (OTH)

AF:

0.0512

AC:

3088

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

2728

5457

8185

10914

13642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1750

3500

5250

7000

8750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0346

AC:

5266

AN:

152268

Hom.:

122

Cov.:

AF XY:

0.0355

AC XY:

2641

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0152

AC:

630

AN:

41546

American (AMR)

AF:

0.0322

AC:

493

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0783

AC:

272

AN:

3472

East Asian (EAS)

AF:

0.0470

AC:

244

AN:

5188

South Asian (SAS)

AF:

0.0941

AC:

453

AN:

4814

European-Finnish (FIN)

AF:

0.0352

AC:

373

AN:

10598

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0390

AC:

2656

AN:

68028

Other (OTH)

AF:

0.0497

AC:

105

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

273

546

818

1091

1364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0403

Hom.:

448

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

May 12, 2022

Rasad Genetic Department, Rasad Pathobiology and Genetic Laboratory

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

(source)

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;.

PhyloP100

2.3

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

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over