rs2076059

Positions:

• chr1-169729780-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000450.2(SELE):​c.716-107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 972,372 control chromosomes in the GnomAD database, including 71,265 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 0.36 (10024 hom., cov: 32)
  • Exomes 𝑓: 0.38 (61241 hom.)
• Consequence: SELE NM_000450.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELE	NM_000450.2	c.716-107G>A		intron_variant		ENST00000333360.12	NP_000441.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELE	ENST00000333360.12	c.716-107G>A		intron_variant		1	NM_000450.2	ENSP00000331736	P1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53986 AN: 151910 Hom.: 10024 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.379 AC: 310918 AN: 820346 Hom.: 61241 AF XY: 0.380 AC XY: 160183 AN XY: 421146

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.437

Gnomad4 EAS exome AF: 0.113

Gnomad4 SAS exome AF: 0.355

Gnomad4 FIN exome AF: 0.340

Gnomad4 NFE exome AF: 0.404

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.355 AC: 53994 AN: 152026 Hom.: 10024 Cov.: 32 AF XY: 0.351 AC XY: 26092 AN XY: 74290

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.374

Alfa AF: 0.380 Hom.: 1653

Bravo AF: 0.353

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.5
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs2076059; hg19: chr1-169698921; COSMIC: COSV60973851; COSMIC: COSV60973851;