1-169731712-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000450.2(SELE):​c.529+123C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 474,108 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SELE NM_000450.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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.529+123C>G		intron	N/A	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.529+123C>G		intron	N/A	ENSP00000331736.7	P16581
	SELE	ENST00000367776.5	TSL:5	c.529+123C>G		intron	N/A	ENSP00000356750.1	Q5TI73
	SELE	ENST00000367777.5	TSL:5	c.529+123C>G		intron	N/A	ENSP00000356751.1	Q5TI74

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000211 AC: 1 AN: 474108 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 250776

African (AFR) AF: 0.00 AC: 0 AN: 12830

American (AMR) AF: 0.00 AC: 0 AN: 22024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13638

East Asian (EAS) AF: 0.00 AC: 0 AN: 29802

South Asian (SAS) AF: 0.0000211 AC: 1 AN: 47496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2992

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 279610

Other (OTH) AF: 0.00 AC: 0 AN: 26276

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.39
PhyloP100		-1.1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3917454;

hg19: chr1-169700853;