Genetic Variant NM_000450.2:c.530-21T>C (chr1-169730638-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_000450.2(SELE):c.530-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,540,522 control chromosomes in the GnomAD database, including 82 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.013 ( 37 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 45 hom. )

Consequence

SELE
NM_000450.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.85

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:25565): (FIGNL1 interacting regulator of recombination and mitosis)

C1orf112 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 5 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1921/152028) while in subpopulation AFR AF= 0.0433 (1796/41490). AF 95% confidence interval is 0.0416. There are 37 homozygotes in gnomad4. There are 908 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELE	NM_000450.2 link	c.530-21T>C		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.530-21T>C		intron_variant	Intron 4 of 13	1	NM_000450.2	ENSP00000331736.7		P16581

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1906

AN:

151922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00610

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00330

AC:

768

AN:

233076

Hom.:

AF XY:

0.00234

AC XY:

296

AN XY:

126432

show subpopulations

Gnomad AFR exome

AF:

0.0447

Gnomad AMR exome

AF:

0.00196

Gnomad ASJ exome

AF:

0.000221

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000107

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000470

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00136

AC:

1886

AN:

1388494

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

776

AN XY:

689236

show subpopulations

Gnomad4 AFR exome

AF:

0.0476

Gnomad4 AMR exome

AF:

0.00254

Gnomad4 ASJ exome

AF:

0.000166

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000244

Gnomad4 OTH exome

AF:

0.00348

GnomAD4 genome

AF:

0.0126

AC:

1921

AN:

152028

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

908

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0433

Gnomad4 AMR

AF:

0.00609

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00894

Hom.:

Bravo

AF:

0.0149

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.91

BranchPoint Hunter

5.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over