dbSNP rs3917454: SELE:c.529+123C>T (chr1-169731712-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.529+123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 626,050 control chromosomes in the GnomAD database, including 442 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 0.029 ( 106 hom., cov: 31)

Exomes 𝑓: 0.033 ( 336 hom. )

Consequence

SELE
NM_000450.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.07

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0288 (4382/152200) while in subpopulation NFE AF = 0.0455 (3097/67996). AF 95% confidence interval is 0.0442. There are 106 homozygotes in GnomAd4. There are 2043 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 106 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELE	NM_000450.2 link	c.529+123C>T		intron_variant	Intron 4 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.529+123C>T		intron_variant	Intron 4 of 13	1	NM_000450.2	ENSP00000331736.7		P16581

Frequencies

GnomAD3 genomes

AF:

0.0288

AC:

4383

AN:

152082

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00727

Gnomad AMI

AF:

0.0692

Gnomad AMR

AF:

0.0208

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0129

Gnomad FIN

AF:

0.0361

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0456

Gnomad OTH

AF:

0.0282

GnomAD4 exome

AF:

0.0330

AC:

15646

AN:

473850

Hom.:

336

Cov.:

AF XY:

0.0322

AC XY:

8077

AN XY:

250658

show subpopulations

African (AFR)

AF:

0.00608

AC:

AN:

12826

American (AMR)

AF:

0.0159

AC:

350

AN:

22016

Ashkenazi Jewish (ASJ)

AF:

0.0227

AC:

309

AN:

13630

East Asian (EAS)

AF:

0.000134

AC:

AN:

29802

South Asian (SAS)

AF:

0.0152

AC:

724

AN:

47476

European-Finnish (FIN)

AF:

0.0382

AC:

1505

AN:

39414

Middle Eastern (MID)

AF:

0.0207

AC:

AN:

2990

European-Non Finnish (NFE)

AF:

0.0423

AC:

11809

AN:

279426

Other (OTH)

AF:

0.0306

AC:

805

AN:

26270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

681

1363

2044

2726

3407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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:

0.0288

AC:

4382

AN:

152200

Hom.:

106

Cov.:

AF XY:

0.0274

AC XY:

2043

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00725

AC:

301

AN:

41540

American (AMR)

AF:

0.0208

AC:

317

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.0129

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0361

AC:

383

AN:

10606

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0455

AC:

3097

AN:

67996

Other (OTH)

AF:

0.0279

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

220

441

661

882

1102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0362

Hom.:

Bravo

AF:

0.0264

Asia WGS

AF:

0.00549

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.65

(source)

DANN

Benign

0.41

PhyloP100

-1.1

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over