rs1076637

chr1-169728303-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

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=-0.9).
• 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/exons	MANE	UniProt
SELE	NM_000450.2	c.1091-57G>A		intron_variant		ENST00000333360.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELE	ENST00000333360.12	c.1091-57G>A		intron_variant		1	NM_000450.2	P1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34115 AN: 151986 Hom.: 4570 Cov.: 33

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

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.505

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.225 AC: 34160 AN: 152104 Hom.: 4580 Cov.: 33 AF XY: 0.231 AC XY: 17179 AN XY: 74346

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.239

Alfa AF: 0.194 Hom.: 704

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
Dann	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs1076637; hg19: chr1-169697444; COSMIC: COSV60977384; COSMIC: COSV60977384;