15-101277671-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOS	NM_018445.6	c.-254G>A		upstream_gene_variant		ENST00000526049.6	NP_060915.2
SELENOS	NM_203472.3	c.-254G>A		upstream_gene_variant			NP_982298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOS	ENST00000526049.6	c.-254G>A		upstream_gene_variant		1	NM_018445.6	ENSP00000433541.1

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

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.266

Alfa AF: 0.250 Hom.: 967

Bravo AF: 0.243

Asia WGS AF: 0.201 AC: 698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34713741; hg19: chr15-101817876;