1-169728303-C-T

Variant names:

• chr1-169728303-C-T
• rs1076637
• NM_000450.2:c.1091-57G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000450.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELE	NM_000450.2	MANE Select	c.1091-57G>A		intron	N/A	NP_000441.2	P16581

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELE	ENST00000333360.12	TSL:1 MANE Select	c.1091-57G>A		intron	N/A	ENSP00000331736.7	P16581
	SELE	ENST00000367776.5	TSL:5	c.1091-376G>A		intron	N/A	ENSP00000356750.1	Q5TI73
	SELE	ENST00000367777.5	TSL:5	c.1091-57G>A		intron	N/A	ENSP00000356751.1	Q5TI74

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

African (AFR) AF: 0.320 AC: 10194 AN: 31820

American (AMR) AF: 0.383 AC: 15061 AN: 39364

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 4331 AN: 23484

East Asian (EAS) AF: 0.505 AC: 19667 AN: 38966

South Asian (SAS) AF: 0.275 AC: 21700 AN: 78842

European-Finnish (FIN) AF: 0.237 AC: 11801 AN: 49854

Middle Eastern (MID) AF: 0.247 AC: 1364 AN: 5522

European-Non Finnish (NFE) AF: 0.135 AC: 144250 AN: 1071164

Other (OTH) AF: 0.200 AC: 11629 AN: 58036

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

African (AFR) AF: 0.308 AC: 12775 AN: 41468

American (AMR) AF: 0.290 AC: 4432 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 630 AN: 3468

East Asian (EAS) AF: 0.478 AC: 2463 AN: 5150

South Asian (SAS) AF: 0.274 AC: 1323 AN: 4822

European-Finnish (FIN) AF: 0.232 AC: 2456 AN: 10582

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9372 AN: 68010

Other (OTH) AF: 0.239 AC: 504 AN: 2108

Alfa AF: 0.197 Hom.: 742

Bravo AF: 0.238

Asia WGS AF: 0.347 AC: 1207 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.74
DANN	Benign	0.40
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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