rs3917436

Positions:

• chr1-169725478-A-G

Variant summary

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

The NM_000450.2(SELE):​c.*15+251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,908 control chromosomes in the GnomAD database, including 11,058 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 (11058 hom., cov: 32)
• Consequence: SELE NM_000450.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.368

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELE	NM_000450.2	c.*15+251T>C		intron_variant		ENST00000333360.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELE	ENST00000333360.12	c.*15+251T>C		intron_variant		1	NM_000450.2	P1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55175 AN: 151788 Hom.: 11022 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.364 AC: 55266 AN: 151908 Hom.: 11058 Cov.: 32 AF XY: 0.369 AC XY: 27411 AN XY: 74248

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.381

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.257

Gnomad4 OTH AF: 0.376

Alfa AF: 0.345 Hom.: 1990

Bravo AF: 0.377

Asia WGS AF: 0.482 AC: 1678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.51

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: rs3917436; hg19: chr1-169694619;