1-169731361-T-C

Variant names:

• chr1-169731361-T-C
• rs3917412
• NM_000450.2:c.529+474A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000450.2(SELE):​c.529+474A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,966 control chromosomes in the GnomAD database, including 48,806 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 0.79 (48593 hom., cov: 31)
  • Exomes 𝑓: 0.71 (213 hom.)
• Consequence: SELE NM_000450.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 18 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 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.529+474A>G		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.529+474A>G		intron	N/A	ENSP00000331736.7	P16581
	SELE	ENST00000367776.5	TSL:5	c.529+474A>G		intron	N/A	ENSP00000356750.1	Q5TI73
	SELE	ENST00000367777.5	TSL:5	c.529+474A>G		intron	N/A	ENSP00000356751.1	Q5TI74

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120541 AN: 152026 Hom.: 48536 Cov.: 31

Gnomad AFR AF: 0.949

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.799

GnomAD4 exome AF: 0.714 AC: 587 AN: 822 Hom.: 213 AF XY: 0.728 AC XY: 271 AN XY: 372

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.830 AC: 83 AN: 100

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.500 AC: 2 AN: 4

South Asian (SAS) AF: 0.773 AC: 17 AN: 22

European-Finnish (FIN) AF: 0.600 AC: 6 AN: 10

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.692 AC: 450 AN: 650

Other (OTH) AF: 0.824 AC: 28 AN: 34

GnomAD4 genome AF: 0.793 AC: 120657 AN: 152144 Hom.: 48593 Cov.: 31 AF XY: 0.792 AC XY: 58884 AN XY: 74360

African (AFR) AF: 0.949 AC: 39445 AN: 41544

American (AMR) AF: 0.791 AC: 12083 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2796 AN: 3470

East Asian (EAS) AF: 0.711 AC: 3671 AN: 5160

South Asian (SAS) AF: 0.822 AC: 3957 AN: 4816

European-Finnish (FIN) AF: 0.705 AC: 7447 AN: 10562

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48731 AN: 67998

Other (OTH) AF: 0.797 AC: 1683 AN: 2112

Alfa AF: 0.740 Hom.: 55833

Bravo AF: 0.806

Asia WGS AF: 0.768 AC: 2668 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.82
DANN	Benign	0.32
PhyloP100		-1.7
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: rs3917412; hg19: chr1-169700502;