rs5356

Positions:

• chr1-169725777-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000450.2(SELE):​c.1800T>C​(p.Asp600=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,613,678 control chromosomes in the GnomAD database, including 11,027 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 0.11 (1082 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9945 hom.)
• Consequence: SELE NM_000450.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELE	NM_000450.2	c.1800T>C	p.Asp600=	synonymous_variant	13/14	ENST00000333360.12	NP_000441.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELE	ENST00000333360.12	c.1800T>C	p.Asp600=	synonymous_variant	13/14	1	NM_000450.2	ENSP00000331736	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16490 AN: 152104 Hom.: 1078 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.123

GnomAD3 exomes AF: 0.144 AC: 36134 AN: 251026 Hom.: 3331 AF XY: 0.139 AC XY: 18834 AN XY: 135654

Gnomad AFR exome AF: 0.0732

Gnomad AMR exome AF: 0.298

Gnomad ASJ exome AF: 0.0845

Gnomad EAS exome AF: 0.197

Gnomad SAS exome AF: 0.147

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.107 AC: 156859 AN: 1461454 Hom.: 9945 Cov.: 32 AF XY: 0.108 AC XY: 78581 AN XY: 727046

Gnomad4 AFR exome AF: 0.0727

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.0858

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.0932

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.108 AC: 16509 AN: 152224 Hom.: 1082 Cov.: 32 AF XY: 0.111 AC XY: 8243 AN XY: 74412

Gnomad4 AFR AF: 0.0751

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.0957

Gnomad4 OTH AF: 0.122

Alfa AF: 0.106 Hom.: 1354

Bravo AF: 0.114

Asia WGS AF: 0.146 AC: 508 AN: 3478

EpiCase AF: 0.103

EpiControl AF: 0.102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.43
DANN	Benign	0.75

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: rs5356; hg19: chr1-169694918; COSMIC: COSV60973950;