1-169731712-G-A

Variant names:

• chr1-169731712-G-A
• rs3917454
• NM_000450.2:c.529+123C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000450.2(SELE):​c.529+123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 626,050 control chromosomes in the GnomAD database, including 442 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 0.029 (106 hom., cov: 31)
  • Exomes 𝑓: 0.033 (336 hom.)
• Consequence: SELE NM_000450.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 6 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=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0288 (4382/152200) while in subpopulation NFE AF = 0.0455 (3097/67996). AF 95% confidence interval is 0.0442. There are 106 homozygotes in GnomAd4. There are 2043 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 106 gene

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.529+123C>T		intron	N/A	NP_000441.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELE	ENST00000333360.12	TSL:1 MANE Select	c.529+123C>T		intron	N/A	ENSP00000331736.7
	SELE	ENST00000461085.1	TSL:3	n.335C>T		non_coding_transcript_exon	Exon 2 of 2
	SELE	ENST00000367776.5	TSL:5	c.529+123C>T		intron	N/A	ENSP00000356750.1

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4383 AN: 152082 Hom.: 106 Cov.: 31

Gnomad AFR AF: 0.00727

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0129

Gnomad FIN AF: 0.0361

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0456

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.0330 AC: 15646 AN: 473850 Hom.: 336 Cov.: 6 AF XY: 0.0322 AC XY: 8077 AN XY: 250658

African (AFR) AF: 0.00608 AC: 78 AN: 12826

American (AMR) AF: 0.0159 AC: 350 AN: 22016

Ashkenazi Jewish (ASJ) AF: 0.0227 AC: 309 AN: 13630

East Asian (EAS) AF: 0.000134 AC: 4 AN: 29802

South Asian (SAS) AF: 0.0152 AC: 724 AN: 47476

European-Finnish (FIN) AF: 0.0382 AC: 1505 AN: 39414

Middle Eastern (MID) AF: 0.0207 AC: 62 AN: 2990

European-Non Finnish (NFE) AF: 0.0423 AC: 11809 AN: 279426

Other (OTH) AF: 0.0306 AC: 805 AN: 26270

GnomAD4 genome AF: 0.0288 AC: 4382 AN: 152200 Hom.: 106 Cov.: 31 AF XY: 0.0274 AC XY: 2043 AN XY: 74432

African (AFR) AF: 0.00725 AC: 301 AN: 41540

American (AMR) AF: 0.0208 AC: 317 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0129 AC: 62 AN: 4816

European-Finnish (FIN) AF: 0.0361 AC: 383 AN: 10606

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0455 AC: 3097 AN: 67996

Other (OTH) AF: 0.0279 AC: 59 AN: 2114

Alfa AF: 0.0362 Hom.: 28

Bravo AF: 0.0264

Asia WGS AF: 0.00549 AC: 19 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.65
DANN	Benign	0.41
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs3917454; hg19: chr1-169700853;