NM_000450.2:c.38-139T>C

Variant names:

• chr1-169733137-A-G
• rs3917406
• NM_000450.2:c.38-139T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000450.2(SELE):​c.38-139T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 850,294 control chromosomes in the GnomAD database, including 35,064 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7403 hom., cov: 32)
  • Exomes 𝑓: 0.27 (27661 hom.)
• Consequence: SELE NM_000450.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35
• Publications: 9 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-169733137-A-G is Benign according to our data. Variant chr1-169733137-A-G is described in ClinVar as Benign. ClinVar VariationId is 1684529.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELE	NM_000450.2	c.38-139T>C		intron_variant	Intron 2 of 13	ENST00000333360.12	NP_000441.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELE	ENST00000333360.12	c.38-139T>C		intron_variant	Intron 2 of 13	1	NM_000450.2	ENSP00000331736.7

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45997 AN: 152006 Hom.: 7390 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.328

GnomAD4 exome AF: 0.267 AC: 186101 AN: 698170 Hom.: 27661 AF XY: 0.269 AC XY: 95482 AN XY: 354490

African (AFR) AF: 0.349 AC: 6059 AN: 17346

American (AMR) AF: 0.403 AC: 5775 AN: 14334

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 4789 AN: 14928

East Asian (EAS) AF: 0.535 AC: 17215 AN: 32152

South Asian (SAS) AF: 0.346 AC: 15080 AN: 43530

European-Finnish (FIN) AF: 0.315 AC: 9627 AN: 30544

Middle Eastern (MID) AF: 0.345 AC: 1011 AN: 2928

European-Non Finnish (NFE) AF: 0.230 AC: 116685 AN: 508432

Other (OTH) AF: 0.290 AC: 9860 AN: 33976

GnomAD4 genome AF: 0.303 AC: 46057 AN: 152124 Hom.: 7403 Cov.: 32 AF XY: 0.307 AC XY: 22819 AN XY: 74358

African (AFR) AF: 0.347 AC: 14412 AN: 41514

American (AMR) AF: 0.355 AC: 5420 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1157 AN: 3468

East Asian (EAS) AF: 0.497 AC: 2570 AN: 5176

South Asian (SAS) AF: 0.349 AC: 1681 AN: 4822

European-Finnish (FIN) AF: 0.303 AC: 3204 AN: 10570

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16592 AN: 67982

Other (OTH) AF: 0.330 AC: 695 AN: 2108

Alfa AF: 0.276 Hom.: 950

Bravo AF: 0.313

Asia WGS AF: 0.395 AC: 1374 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Coronary artery disorder Benign:1

May 12, 2022

Rasad Genetic Department, Rasad Pathobiology and Genetic Laboratory

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.43
DANN	Benign	0.31
PhyloP100		-1.4
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: rs3917406; hg19: chr1-169702278;