1-169729780-C-T

Variant names:

• chr1-169729780-C-T
• rs2076059
• NM_000450.2:c.716-107G>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.716-107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 972,372 control chromosomes in the GnomAD database, including 71,265 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 (10024 hom., cov: 32)
  • Exomes 𝑓: 0.38 (61241 hom.)
• Consequence: SELE NM_000450.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 16 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=-0.69).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELE	NM_000450.2	c.716-107G>A		intron_variant	Intron 5 of 13	ENST00000333360.12	NP_000441.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELE	ENST00000333360.12	c.716-107G>A		intron_variant	Intron 5 of 13	1	NM_000450.2	ENSP00000331736.7

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53986 AN: 151910 Hom.: 10024 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.379 AC: 310918 AN: 820346 Hom.: 61241 AF XY: 0.380 AC XY: 160183 AN XY: 421146

African (AFR) AF: 0.279 AC: 5516 AN: 19736

American (AMR) AF: 0.346 AC: 10553 AN: 30488

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 7441 AN: 17046

East Asian (EAS) AF: 0.113 AC: 4095 AN: 36256

South Asian (SAS) AF: 0.355 AC: 20599 AN: 58014

European-Finnish (FIN) AF: 0.340 AC: 14056 AN: 41296

Middle Eastern (MID) AF: 0.466 AC: 2007 AN: 4306

European-Non Finnish (NFE) AF: 0.404 AC: 232061 AN: 574570

Other (OTH) AF: 0.378 AC: 14590 AN: 38634

GnomAD4 genome AF: 0.355 AC: 53994 AN: 152026 Hom.: 10024 Cov.: 32 AF XY: 0.351 AC XY: 26092 AN XY: 74290

African (AFR) AF: 0.281 AC: 11670 AN: 41480

American (AMR) AF: 0.375 AC: 5732 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1466 AN: 3468

East Asian (EAS) AF: 0.134 AC: 693 AN: 5170

South Asian (SAS) AF: 0.343 AC: 1652 AN: 4810

European-Finnish (FIN) AF: 0.336 AC: 3548 AN: 10558

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 27985 AN: 67944

Other (OTH) AF: 0.374 AC: 787 AN: 2106

Alfa AF: 0.377 Hom.: 1685

Bravo AF: 0.353

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.5
DANN	Benign	0.72
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2076059; hg19: chr1-169698921; COSMIC: COSV60973851; COSMIC: COSV60973851;