rs5368

Variant names:

• chr1-169727805-G-A
• rs5368
• NM_000450.2:c.1402C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-169727805-G-A
• chr1-169727805-G-C
• chr1-169727805-G-T

Variant summary

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

The NM_000450.2(SELE):​c.1402C>T​(p.His468Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,613,874 control chromosomes in the GnomAD database, including 11,098 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.11 (1089 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10009 hom.)
• Consequence: SELE NM_000450.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.480
• Publications: 65 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 (MetaRNN=0.0035199225).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 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.1402C>T	p.His468Tyr	missense	Exon 9 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.1402C>T	p.His468Tyr	missense	Exon 9 of 14	ENSP00000331736.7	P16581
	SELE	ENST00000367776.5	TSL:5	c.1213C>T	p.His405Tyr	missense	Exon 7 of 12	ENSP00000356750.1	Q5TI73
	SELE	ENST00000367775.5	TSL:5	c.1027C>T	p.His343Tyr	missense	Exon 6 of 11	ENSP00000356749.1	Q5TI75

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16504 AN: 152064 Hom.: 1084 Cov.: 32

Gnomad AFR AF: 0.0752

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0958

Gnomad OTH AF: 0.124

GnomAD2 exomes AF: 0.145 AC: 36320 AN: 251050 AF XY: 0.139

Gnomad AFR exome AF: 0.0732

Gnomad AMR exome AF: 0.297

Gnomad ASJ exome AF: 0.0843

Gnomad EAS exome AF: 0.208

Gnomad FIN exome AF: 0.138

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.108 AC: 157241 AN: 1461692 Hom.: 10009 Cov.: 33 AF XY: 0.108 AC XY: 78778 AN XY: 727142

African (AFR) AF: 0.0727 AC: 2433 AN: 33474

American (AMR) AF: 0.289 AC: 12906 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0857 AC: 2239 AN: 26132

East Asian (EAS) AF: 0.208 AC: 8249 AN: 39694

South Asian (SAS) AF: 0.146 AC: 12622 AN: 86248

European-Finnish (FIN) AF: 0.142 AC: 7565 AN: 53416

Middle Eastern (MID) AF: 0.137 AC: 791 AN: 5764

European-Non Finnish (NFE) AF: 0.0933 AC: 103740 AN: 1111856

Other (OTH) AF: 0.111 AC: 6696 AN: 60390

GnomAD4 genome AF: 0.109 AC: 16524 AN: 152182 Hom.: 1089 Cov.: 32 AF XY: 0.111 AC XY: 8253 AN XY: 74380

African (AFR) AF: 0.0751 AC: 3121 AN: 41542

American (AMR) AF: 0.195 AC: 2987 AN: 15294

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

East Asian (EAS) AF: 0.209 AC: 1077 AN: 5160

South Asian (SAS) AF: 0.141 AC: 677 AN: 4816

European-Finnish (FIN) AF: 0.137 AC: 1445 AN: 10568

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

European-Non Finnish (NFE) AF: 0.0958 AC: 6513 AN: 68012

Other (OTH) AF: 0.122 AC: 258 AN: 2114

Alfa AF: 0.106 Hom.: 3479

Bravo AF: 0.115

TwinsUK AF: 0.0965 AC: 358

ALSPAC AF: 0.0960 AC: 370

ESP6500AA AF: 0.0778 AC: 343

ESP6500EA AF: 0.0949 AC: 816

ExAC AF: 0.139 AC: 16905

Asia WGS AF: 0.148 AC: 513 AN: 3476

EpiCase AF: 0.103

EpiControl AF: 0.102

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	IgA nephropathy, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T
Eigen	Benign	0.079
Eigen_PC	Benign	0.0065
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.064	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.48
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.18
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.039	D
Polyphen		0.94	P
Vest4		0.098
MPC		0.23
ClinPred		0.065	T
GERP RS		5.7
gMVP		0.18
Mutation Taster		=97/3	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: rs5368; hg19: chr1-169696946; COSMIC: COSV60973959; COSMIC: COSV60973959;