chr1-169733564-G-A

Variant names:

• chr1-169733564-G-A
• rs932307
• NM_000450.2:c.37+12C>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.37+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,608,712 control chromosomes in the GnomAD database, including 63,081 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 0.30 (7422 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55659 hom.)
• Consequence: SELE NM_000450.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 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.37+12C>T		intron	N/A	NP_000441.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELE	ENST00000333360.12	TSL:1 MANE Select	c.37+12C>T		intron	N/A	ENSP00000331736.7
	SELE	ENST00000367776.5	TSL:5	c.37+12C>T		intron	N/A	ENSP00000356750.1
	SELE	ENST00000367777.5	TSL:5	c.37+12C>T		intron	N/A	ENSP00000356751.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46044 AN: 151910 Hom.: 7408 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.359

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.329

GnomAD2 exomes AF: 0.325 AC: 81642 AN: 250930 AF XY: 0.320

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.326

Gnomad EAS exome AF: 0.503

Gnomad FIN exome AF: 0.305

Gnomad NFE exome AF: 0.253

Gnomad OTH exome AF: 0.331

GnomAD4 exome AF: 0.265 AC: 386417 AN: 1456684 Hom.: 55659 Cov.: 31 AF XY: 0.268 AC XY: 194476 AN XY: 724978

African (AFR) AF: 0.357 AC: 11904 AN: 33382

American (AMR) AF: 0.432 AC: 19332 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8457 AN: 26092

East Asian (EAS) AF: 0.533 AC: 21154 AN: 39674

South Asian (SAS) AF: 0.354 AC: 30484 AN: 86124

European-Finnish (FIN) AF: 0.312 AC: 16649 AN: 53388

Middle Eastern (MID) AF: 0.362 AC: 2086 AN: 5756

European-Non Finnish (NFE) AF: 0.233 AC: 258521 AN: 1107308

Other (OTH) AF: 0.296 AC: 17830 AN: 60256

GnomAD4 genome AF: 0.303 AC: 46105 AN: 152028 Hom.: 7422 Cov.: 32 AF XY: 0.307 AC XY: 22845 AN XY: 74316

African (AFR) AF: 0.349 AC: 14449 AN: 41432

American (AMR) AF: 0.355 AC: 5429 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1158 AN: 3472

East Asian (EAS) AF: 0.497 AC: 2566 AN: 5166

South Asian (SAS) AF: 0.349 AC: 1676 AN: 4806

European-Finnish (FIN) AF: 0.304 AC: 3214 AN: 10572

Middle Eastern (MID) AF: 0.366 AC: 106 AN: 290

European-Non Finnish (NFE) AF: 0.244 AC: 16593 AN: 67982

Other (OTH) AF: 0.330 AC: 696 AN: 2110

Alfa AF: 0.281 Hom.: 2009

Bravo AF: 0.313

Asia WGS AF: 0.394 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.58
PhyloP100		-0.58
PromoterAI		0.026	Neutral
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: rs932307; hg19: chr1-169702705; COSMIC: COSV60974529; COSMIC: COSV60974529;