rs10489181

Positions:

• chr1-169743456-T-C

Variant summary

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

The ENST00000609271.1(SELE):​c.-201-9333A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,116 control chromosomes in the GnomAD database, including 3,978 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 0.20 (3978 hom., cov: 31)
• Consequence: SELE ENST00000609271.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELE	ENST00000609271.1	c.-201-9333A>G		intron_variant		4		ENSP00000476784
FIRRM	ENST00000498289.5	n.852-40355T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30306 AN: 151998 Hom.: 3963 Cov.: 31

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.200 AC: 30379 AN: 152116 Hom.: 3978 Cov.: 31 AF XY: 0.205 AC XY: 15241 AN XY: 74382

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.0987

Gnomad4 OTH AF: 0.205

Alfa AF: 0.140 Hom.: 405

Bravo AF: 0.216

Asia WGS AF: 0.265 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.036
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10489181; hg19: chr1-169712597;