chr1-169727504-G-A

Variant names:

• chr1-169727504-G-A
• rs763174875
• NM_000450.2:c.1490C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000450.2(SELE):​c.1490C>T​(p.Ala497Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: SELE NM_000450.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.57
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0987255).

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.1490C>T	p.Ala497Val	missense	Exon 10 of 14	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.1490C>T	p.Ala497Val	missense	Exon 10 of 14	ENSP00000331736.7	P16581
	SELE	ENST00000367776.5	TSL:5	c.1301C>T	p.Ala434Val	missense	Exon 8 of 12	ENSP00000356750.1	Q5TI73
	SELE	ENST00000367777.5	TSL:5	c.1301C>T	p.Ala434Val	missense	Exon 8 of 12	ENSP00000356751.1	Q5TI74

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000362 AC: 9 AN: 248846 AF XY: 0.0000520

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000358

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.0000315 AC: 46 AN: 1461476 Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27 AN XY: 727008

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.0000672 AC: 3 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86166

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1111872

Other (OTH) AF: 0.0000497 AC: 3 AN: 60370

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41460

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000579 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.9
DANN	Benign	0.97
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.70	N
PhyloP100		-2.6
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.053
Sift	Benign	0.26	T
Sift4G	Benign	0.28	T
Polyphen		0.60	P
Vest4		0.16
MVP		0.46
MPC		0.057
ClinPred		0.080	T
GERP RS		0.42
gMVP		0.16
Mutation Taster		=97/3	polymorphism

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: rs763174875; hg19: chr1-169696645;