15-101277522-C-T

Position:

• chr15-101277522-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.152 in 1,292,772 control chromosomes in the GnomAD database, including 19,756 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 (6415 hom., cov: 32)
  • Exomes 𝑓: 0.14 (13341 hom.)
• Consequence: intergenic_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

Genes affected

(HGNC:):

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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.101277522C>T		intergenic_region
SELENOS	NM_018445.6	c.-105G>A		upstream_gene_variant		ENST00000526049.6	NP_060915.2
SELENOS	NM_203472.3	c.-105G>A		upstream_gene_variant			NP_982298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELENOS	ENST00000526049.6	c.-105G>A		upstream_gene_variant		1	NM_018445.6	ENSP00000433541.1
SELENOS	ENST00000529968.1	n.-22G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35853 AN: 151952 Hom.: 6400 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0808

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.141 AC: 160830 AN: 1140710 Hom.: 13341 Cov.: 28 AF XY: 0.139 AC XY: 76281 AN XY: 548070

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.0593

Gnomad4 SAS exome AF: 0.0682

Gnomad4 FIN exome AF: 0.153

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.236 AC: 35910 AN: 152062 Hom.: 6415 Cov.: 32 AF XY: 0.231 AC XY: 17202 AN XY: 74346

Gnomad4 AFR AF: 0.500

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0802

Gnomad4 SAS AF: 0.0600

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.222

Alfa AF: 0.182 Hom.: 454

Bravo AF: 0.254

Asia WGS AF: 0.104 AC: 360 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.8
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: rs28665122; hg19: chr15-101817727;