chr1-169731919-T-G

Variant names:

• chr1-169731919-T-G
• rs5361
• NM_000450.2:c.445A>C

Variant summary

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

The NM_000450.2(SELE):​c.445A>C​(p.Ser149Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,612,270 control chromosomes in the GnomAD database, including 7,453 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 0.078 (562 hom., cov: 31)
  • Exomes 𝑓: 0.093 (6891 hom.)
• Consequence: SELE NM_000450.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.34
• Publications: 216 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=0.0030622482).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 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.445A>C	p.Ser149Arg	missense	Exon 4 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.445A>C	p.Ser149Arg	missense	Exon 4 of 14	ENSP00000331736.7	P16581
	SELE	ENST00000367776.5	TSL:5	c.445A>C	p.Ser149Arg	missense	Exon 3 of 12	ENSP00000356750.1	Q5TI73
	SELE	ENST00000367777.5	TSL:5	c.445A>C	p.Ser149Arg	missense	Exon 3 of 12	ENSP00000356751.1	Q5TI74

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11854 AN: 152106 Hom.: 562 Cov.: 31

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0647

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.0720

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0856

GnomAD2 exomes AF: 0.0827 AC: 20737 AN: 250828 AF XY: 0.0855

Gnomad AFR exome AF: 0.0367

Gnomad AMR exome AF: 0.0493

Gnomad ASJ exome AF: 0.147

Gnomad EAS exome AF: 0.0137

Gnomad FIN exome AF: 0.0748

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.0984

GnomAD4 exome AF: 0.0934 AC: 136412 AN: 1460046 Hom.: 6891 Cov.: 30 AF XY: 0.0940 AC XY: 68287 AN XY: 726384

African (AFR) AF: 0.0362 AC: 1212 AN: 33444

American (AMR) AF: 0.0514 AC: 2300 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 3684 AN: 26108

East Asian (EAS) AF: 0.0273 AC: 1081 AN: 39650

South Asian (SAS) AF: 0.0810 AC: 6986 AN: 86220

European-Finnish (FIN) AF: 0.0779 AC: 4158 AN: 53388

Middle Eastern (MID) AF: 0.115 AC: 662 AN: 5764

European-Non Finnish (NFE) AF: 0.0996 AC: 110579 AN: 1110458

Other (OTH) AF: 0.0953 AC: 5750 AN: 60310

GnomAD4 genome AF: 0.0779 AC: 11856 AN: 152224 Hom.: 562 Cov.: 31 AF XY: 0.0757 AC XY: 5634 AN XY: 74440

African (AFR) AF: 0.0389 AC: 1617 AN: 41540

American (AMR) AF: 0.0646 AC: 988 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3466

East Asian (EAS) AF: 0.0168 AC: 87 AN: 5168

South Asian (SAS) AF: 0.0743 AC: 358 AN: 4820

European-Finnish (FIN) AF: 0.0720 AC: 764 AN: 10610

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7218 AN: 68016

Other (OTH) AF: 0.0838 AC: 177 AN: 2112

Alfa AF: 0.0967 Hom.: 3722

Bravo AF: 0.0748

TwinsUK AF: 0.0957 AC: 355

ALSPAC AF: 0.0999 AC: 385

ESP6500AA AF: 0.0413 AC: 182

ESP6500EA AF: 0.106 AC: 909

ExAC AF: 0.0841 AC: 10215

Asia WGS AF: 0.0470 AC: 165 AN: 3478

EpiCase AF: 0.108

EpiControl AF: 0.105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	D
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0031	T
MetaSVM	Uncertain	0.53	D
MutationAssessor	Benign	1.6	L
PhyloP100		2.3
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.24		Loss of glycosylation at S149 (P = 0.0086)
MPC		0.37
ClinPred		0.011	T
GERP RS		4.4
gMVP		0.54
Mutation Taster		=97/3	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: rs5361; hg19: chr1-169701060; COSMIC: COSV60974844; COSMIC: COSV60974844;