rs12408179

Positions:

• chr1-169738986-T-C

Variant summary

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

The ENST00000609271.1(SELE):​c.-201-4863A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,208 control chromosomes in the GnomAD database, including 1,508 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 0.14 (1508 hom., cov: 32)
• Consequence: SELE ENST00000609271.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELE	ENST00000609271.1	c.-201-4863A>G		intron_variant		4
FIRRM	ENST00000498289.5	n.852-44825T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20570 AN: 152090 Hom.: 1508 Cov.: 32

Gnomad AFR AF: 0.0912

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.135 AC: 20586 AN: 152208 Hom.: 1508 Cov.: 32 AF XY: 0.137 AC XY: 10186 AN XY: 74422

Gnomad4 AFR AF: 0.0912

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.130

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.144

Alfa AF: 0.145 Hom.: 370

Bravo AF: 0.135

Asia WGS AF: 0.175 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12408179; hg19: chr1-169708127;