15-101277671-C-T

Variant names:

• chr15-101277671-C-T
• rs34713741
• NM_018445.6:c.-254G>A

Variant summary

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

The NM_018445.6(SELENOS):​c.-254G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,050 control chromosomes in the GnomAD database, including 4,705 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 0.24 (4705 hom., cov: 33)
• Consequence: SELENOS NM_018445.6 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 30 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.316 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.-254G>A		upstream_gene	N/A	NP_060915.2
	SELENOS	NM_203472.3		c.-254G>A		upstream_gene	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.-254G>A		upstream_gene	N/A	ENSP00000433541.1	Q9BQE4
	SELENOS	ENST00000398226.8	TSL:1	c.-254G>A		upstream_gene	N/A	ENSP00000381282.3	Q9BQE4
	SELENOS	ENST00000526043.1	TSL:2	n.-200G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36383 AN: 151938 Hom.: 4703 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.239 AC: 36395 AN: 152050 Hom.: 4705 Cov.: 33 AF XY: 0.240 AC XY: 17817 AN XY: 74324

African (AFR) AF: 0.142 AC: 5903 AN: 41512

American (AMR) AF: 0.323 AC: 4941 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1022 AN: 3468

East Asian (EAS) AF: 0.250 AC: 1290 AN: 5164

South Asian (SAS) AF: 0.188 AC: 907 AN: 4830

European-Finnish (FIN) AF: 0.267 AC: 2809 AN: 10526

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18706 AN: 67942

Other (OTH) AF: 0.266 AC: 561 AN: 2112

Alfa AF: 0.259 Hom.: 8031

Bravo AF: 0.243

Asia WGS AF: 0.201 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.92
PhyloP100		-2.0
PromoterAI		0.018	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34713741; hg19: chr15-101817876;