rs9874

Variant names:

• chr15-101271199-T-C
• rs9874
• ENST00000398226.8:c.*454A>G

Variant summary

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

The ENST00000398226.8(SELENOS):​c.*454A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,182 control chromosomes in the GnomAD database, including 5,579 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 0.23 (5579 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: SELENOS ENST00000398226.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375
• Publications: 18 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOS	NM_203472.3	c.*460A>G		3_prime_UTR_variant	Exon 7 of 7		NP_982298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOS	ENST00000398226.8	c.*454A>G		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000381282.3
SELENOS	ENST00000531964.5	c.*454A>G		downstream_gene_variant		3		ENSP00000433803.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34287 AN: 152064 Hom.: 5568 Cov.: 33

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.0668

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.196

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.226 AC: 34334 AN: 152182 Hom.: 5579 Cov.: 33 AF XY: 0.222 AC XY: 16543 AN XY: 74404

African (AFR) AF: 0.466 AC: 19311 AN: 41472

American (AMR) AF: 0.136 AC: 2076 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3470

East Asian (EAS) AF: 0.0160 AC: 83 AN: 5186

South Asian (SAS) AF: 0.0667 AC: 322 AN: 4828

European-Finnish (FIN) AF: 0.190 AC: 2017 AN: 10594

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9451 AN: 68016

Other (OTH) AF: 0.201 AC: 424 AN: 2114

Alfa AF: 0.157 Hom.: 2511

Bravo AF: 0.233

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.40
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs9874; hg19: chr15-101811404;