Genetic Variant SELE:c.1091-57G>A (chr1-169728303-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000450.2(SELE):c.1091-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,549,156 control chromosomes in the GnomAD database, including 30,321 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4580 hom., cov: 33)

Exomes 𝑓: 0.17 ( 25741 hom. )

Consequence

SELE
NM_000450.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.550

Publications

10 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELE	NM_000450.2 link	c.1091-57G>A		intron_variant	Intron 7 of 13	ENST00000333360.12	NP_000441.2	P16581

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELE	ENST00000333360.12 link	c.1091-57G>A		intron_variant	Intron 7 of 13	1	NM_000450.2	ENSP00000331736.7		P16581

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34115

AN:

151986

Hom.:

4570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.478

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.242

GnomAD4 exome

AF:

0.172

AC:

239997

AN:

1397052

Hom.:

25741

AF XY:

0.174

AC XY:

120685

AN XY:

692872

show subpopulations

African (AFR)

AF:

0.320

AC:

10194

AN:

31820

American (AMR)

AF:

0.383

AC:

15061

AN:

39364

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

4331

AN:

23484

East Asian (EAS)

AF:

0.505

AC:

19667

AN:

38966

South Asian (SAS)

AF:

0.275

AC:

21700

AN:

78842

European-Finnish (FIN)

AF:

0.237

AC:

11801

AN:

49854

Middle Eastern (MID)

AF:

0.247

AC:

1364

AN:

5522

European-Non Finnish (NFE)

AF:

0.135

AC:

144250

AN:

1071164

Other (OTH)

AF:

0.200

AC:

11629

AN:

58036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

9120

18240

27361

36481

45601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5640

11280

16920

22560

28200

<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:

0.225

AC:

34160

AN:

152104

Hom.:

4580

Cov.:

AF XY:

0.231

AC XY:

17179

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.308

AC:

12775

AN:

41468

American (AMR)

AF:

0.290

AC:

4432

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

630

AN:

3468

East Asian (EAS)

AF:

0.478

AC:

2463

AN:

5150

South Asian (SAS)

AF:

0.274

AC:

1323

AN:

4822

European-Finnish (FIN)

AF:

0.232

AC:

2456

AN:

10582

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9372

AN:

68010

Other (OTH)

AF:

0.239

AC:

504

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1309

2617

3926

5234

6543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.197

Hom.:

742

Bravo

AF:

0.238

Asia WGS

AF:

0.347

AC:

1207

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.74

(source)

DANN

Benign

0.40

PhyloP100

-0.55

Mutation Taster

=100/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over