chr1-169730638-A-G

Variant names:

• chr1-169730638-A-G
• rs3917420
• NM_000450.2:c.530-21T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The ENST00000333360.12(SELE):​c.530-21T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,540,522 control chromosomes in the GnomAD database, including 82 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.013 (37 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (45 hom.)
• Consequence: SELE ENST00000333360.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• Publications: 2 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 -10 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 5 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0126 (1921/152028) while in subpopulation AFR AF = 0.0433 (1796/41490). AF 95% confidence interval is 0.0416. There are 37 homozygotes in GnomAd4. There are 908 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 37 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000333360.12. 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.530-21T>C		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.530-21T>C		intron	N/A	ENSP00000331736.7
	SELE	ENST00000367776.5	TSL:5	c.530-21T>C		intron	N/A	ENSP00000356750.1
	SELE	ENST00000367777.5	TSL:5	c.530-21T>C		intron	N/A	ENSP00000356751.1

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1906 AN: 151922 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00610

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00330 AC: 768 AN: 233076 AF XY: 0.00234

Gnomad AFR exome AF: 0.0447

Gnomad AMR exome AF: 0.00196

Gnomad ASJ exome AF: 0.000221

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000470

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00136 AC: 1886 AN: 1388494 Hom.: 45 Cov.: 25 AF XY: 0.00113 AC XY: 776 AN XY: 689236

African (AFR) AF: 0.0476 AC: 1530 AN: 32174

American (AMR) AF: 0.00254 AC: 107 AN: 42098

Ashkenazi Jewish (ASJ) AF: 0.000166 AC: 4 AN: 24156

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38676

South Asian (SAS) AF: 0.000174 AC: 13 AN: 74618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50422

Middle Eastern (MID) AF: 0.00128 AC: 7 AN: 5466

European-Non Finnish (NFE) AF: 0.0000244 AC: 26 AN: 1064056

Other (OTH) AF: 0.00348 AC: 198 AN: 56828

GnomAD4 genome AF: 0.0126 AC: 1921 AN: 152028 Hom.: 37 Cov.: 32 AF XY: 0.0122 AC XY: 908 AN XY: 74318

African (AFR) AF: 0.0433 AC: 1796 AN: 41490

American (AMR) AF: 0.00609 AC: 93 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67972

Other (OTH) AF: 0.0114 AC: 24 AN: 2112

Alfa AF: 0.00757 Hom.: 7

Bravo AF: 0.0149

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Benign	0.91
PhyloP100		2.8
BranchPoint Hunter		5.0
Mutation Taster		=100/0	polymorphism

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: rs3917420; hg19: chr1-169699779;