1-169725777-A-G

Variant names:

• chr1-169725777-A-G
• rs5356
• NM_000450.2:c.1800T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000450.2(SELE):​c.1800T>C​(p.Asp600Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,613,678 control chromosomes in the GnomAD database, including 11,027 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 0.11 (1082 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9945 hom.)
• Consequence: SELE NM_000450.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 29 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.192 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELE	NM_000450.2	MANE Select	c.1800T>C	p.Asp600Asp	synonymous	Exon 13 of 14	NP_000441.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELE	ENST00000333360.12	TSL:1 MANE Select	c.1800T>C	p.Asp600Asp	synonymous	Exon 13 of 14	ENSP00000331736.7
	SELE	ENST00000367776.5	TSL:5	c.1611T>C	p.Asp537Asp	synonymous	Exon 11 of 12	ENSP00000356750.1
	SELE	ENST00000367777.5	TSL:5	c.1611T>C	p.Asp537Asp	synonymous	Exon 11 of 12	ENSP00000356751.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16490 AN: 152104 Hom.: 1078 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0957

Gnomad OTH AF: 0.123

GnomAD2 exomes AF: 0.144 AC: 36134 AN: 251026 AF XY: 0.139

Gnomad AFR exome AF: 0.0732

Gnomad AMR exome AF: 0.298

Gnomad ASJ exome AF: 0.0845

Gnomad EAS exome AF: 0.197

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.107 AC: 156859 AN: 1461454 Hom.: 9945 Cov.: 32 AF XY: 0.108 AC XY: 78581 AN XY: 727046

African (AFR) AF: 0.0727 AC: 2434 AN: 33470

American (AMR) AF: 0.290 AC: 12952 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0858 AC: 2241 AN: 26128

East Asian (EAS) AF: 0.201 AC: 7971 AN: 39662

South Asian (SAS) AF: 0.146 AC: 12606 AN: 86238

European-Finnish (FIN) AF: 0.142 AC: 7558 AN: 53402

Middle Eastern (MID) AF: 0.137 AC: 792 AN: 5766

European-Non Finnish (NFE) AF: 0.0932 AC: 103644 AN: 1111686

Other (OTH) AF: 0.110 AC: 6661 AN: 60384

GnomAD4 genome AF: 0.108 AC: 16509 AN: 152224 Hom.: 1082 Cov.: 32 AF XY: 0.111 AC XY: 8243 AN XY: 74412

African (AFR) AF: 0.0751 AC: 3122 AN: 41544

American (AMR) AF: 0.198 AC: 3029 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3472

East Asian (EAS) AF: 0.198 AC: 1024 AN: 5174

South Asian (SAS) AF: 0.141 AC: 679 AN: 4830

European-Finnish (FIN) AF: 0.137 AC: 1447 AN: 10600

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.0957 AC: 6505 AN: 67994

Other (OTH) AF: 0.122 AC: 257 AN: 2112

Alfa AF: 0.106 Hom.: 1690

Bravo AF: 0.114

Asia WGS AF: 0.146 AC: 508 AN: 3478

EpiCase AF: 0.103

EpiControl AF: 0.102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.43
DANN	Benign	0.75
PhyloP100		-1.1
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: rs5356; hg19: chr1-169694918; COSMIC: COSV60973950;