Genetic Variant SELE:c.*16-200C>T (chr1-169724709-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000450.2(SELE):c.*16-200C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0314 in 152,230 control chromosomes in the GnomAD database, including 112 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 0.031 ( 112 hom., cov: 32)

Consequence

SELE
NM_000450.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.707

Publications

5 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=-0.94).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0314 (4786/152230) while in subpopulation NFE AF = 0.0488 (3316/68018). AF 95% confidence interval is 0.0474. There are 112 homozygotes in GnomAd4. There are 2201 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 112 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELE	NM_000450.2 link	c.*16-200C>T		intron_variant	Intron 13 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.*16-200C>T		intron_variant	Intron 13 of 13	1	NM_000450.2	ENSP00000331736.7		P16581

Frequencies

GnomAD3 genomes

AF:

0.0315

AC:

4788

AN:

152112

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00925

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.0364

Gnomad ASJ

AF:

0.0565

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00787

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0488

Gnomad OTH

AF:

0.0330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0314

AC:

4786

AN:

152230

Hom.:

112

Cov.:

AF XY:

0.0296

AC XY:

2201

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00922

AC:

383

AN:

41546

American (AMR)

AF:

0.0363

AC:

555

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0565

AC:

196

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00787

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0172

AC:

182

AN:

10582

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0488

AC:

3316

AN:

68018

Other (OTH)

AF:

0.0327

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

242

485

727

970

1212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0297

Hom.:

Bravo

AF:

0.0332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.44

(source)

DANN

Benign

0.22

PhyloP100

-0.71

Mutation Taster

=100/0

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over