chr1-169731712-G-A

Position:

• chr1-169731712-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000450.2(SELE):​c.529+123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 626,050 control chromosomes in the GnomAD database, including 442 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 0.029 (106 hom., cov: 31)
  • Exomes 𝑓: 0.033 (336 hom.)
• Consequence: SELE NM_000450.2 intron
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0288 (4382/152200) while in subpopulation NFE AF= 0.0455 (3097/67996). AF 95% confidence interval is 0.0442. There are 106 homozygotes in gnomad4. There are 2043 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 106 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELE	NM_000450.2	c.529+123C>T		intron_variant		ENST00000333360.12	NP_000441.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELE	ENST00000333360.12	c.529+123C>T		intron_variant		1	NM_000450.2	ENSP00000331736	P1

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4383 AN: 152082 Hom.: 106 Cov.: 31

Gnomad AFR AF: 0.00727

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0129

Gnomad FIN AF: 0.0361

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0456

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.0330 AC: 15646 AN: 473850 Hom.: 336 Cov.: 6 AF XY: 0.0322 AC XY: 8077 AN XY: 250658

Gnomad4 AFR exome AF: 0.00608

Gnomad4 AMR exome AF: 0.0159

Gnomad4 ASJ exome AF: 0.0227

Gnomad4 EAS exome AF: 0.000134

Gnomad4 SAS exome AF: 0.0152

Gnomad4 FIN exome AF: 0.0382

Gnomad4 NFE exome AF: 0.0423

Gnomad4 OTH exome AF: 0.0306

GnomAD4 genome AF: 0.0288 AC: 4382 AN: 152200 Hom.: 106 Cov.: 31 AF XY: 0.0274 AC XY: 2043 AN XY: 74432

Gnomad4 AFR AF: 0.00725

Gnomad4 AMR AF: 0.0208

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.0361

Gnomad4 NFE AF: 0.0455

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0362 Hom.: 28

Bravo AF: 0.0264

Asia WGS AF: 0.00549 AC: 19 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.65
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs3917454; hg19: chr1-169700853;