rs12917258

Variant names:

• chr15-101273134-C-G
• rs12917258
• NM_018445.6:c.485-278G>C

Variant summary

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

The NM_018445.6(SELENOS):​c.485-278G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,082 control chromosomes in the GnomAD database, including 3,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.19 (3849 hom., cov: 32)
• Consequence: SELENOS NM_018445.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 9 publications found

Genes affected

SELENOS (HGNC:30396): (selenoprotein S) This gene encodes a transmembrane protein that is localized in the endoplasmic reticulum (ER). It is involved in the degradation process of misfolded proteins in the ER, and may also have a role in inflammation control. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Two additional phylogenetically conserved stem-loop structures (Stem-loop 1 and Stem-loop 2) in the 3' UTR of this mRNA have been shown to function as modulators of Sec insertion. An alternatively spliced transcript variant, lacking the SECIS element and encoding a non-Sec containing shorter isoform, has been described for this gene (PMID:23614019). [provided by RefSeq, Jul 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018445.6. 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
	SELENOS	NM_018445.6	MANE Select	c.485-278G>C		intron	N/A	NP_060915.2
	SELENOS	NM_203472.3		c.485-278G>C		intron	N/A	NP_982298.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOS	ENST00000526049.6	TSL:1 MANE Select	c.485-278G>C		intron	N/A	ENSP00000433541.1	Q9BQE4
	SELENOS	ENST00000398226.8	TSL:1	c.485-278G>C		intron	N/A	ENSP00000381282.3	Q9BQE4
	SELENOS	ENST00000528346.1	TSL:3	c.605-278G>C		intron	N/A	ENSP00000434842.1	E9PN30

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29460 AN: 151966 Hom.: 3850 Cov.: 32

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.232

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.194 AC: 29458 AN: 152082 Hom.: 3849 Cov.: 32 AF XY: 0.187 AC XY: 13911 AN XY: 74354

African (AFR) AF: 0.0504 AC: 2093 AN: 41504

American (AMR) AF: 0.227 AC: 3466 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1019 AN: 3458

East Asian (EAS) AF: 0.00945 AC: 49 AN: 5184

South Asian (SAS) AF: 0.116 AC: 560 AN: 4818

European-Finnish (FIN) AF: 0.184 AC: 1941 AN: 10576

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19606 AN: 67944

Other (OTH) AF: 0.229 AC: 483 AN: 2108

Alfa AF: 0.237 Hom.: 620

Bravo AF: 0.191

Asia WGS AF: 0.0890 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.64
PhyloP100		0.63
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: rs12917258; hg19: chr15-101813339;