15-101272190-A-G

Variant names:

• chr15-101272190-A-G
• rs4965373
• ENST00000398226.7:c.*8-545T>C

Variant summary

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

The NM_203472.3(SELENOS):​c.*14-545T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 152,270 control chromosomes in the GnomAD database, including 42,736 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 0.74 (42736 hom., cov: 35)
  • Failed GnomAD Quality Control
• Consequence: SELENOS NM_203472.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556

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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOS	NM_203472.3	c.*14-545T>C		intron_variant	Intron 6 of 6		NP_982298.2
SELENOS	NM_018445.6	c.*581T>C		downstream_gene_variant		ENST00000526049.6	NP_060915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOS	ENST00000398226.7	c.*8-545T>C		intron_variant	Intron 6 of 6	1		ENSP00000381282.3
SELENOS	ENST00000531964.5	c.*8-545T>C		intron_variant	Intron 6 of 6	3		ENSP00000433803.1
SELENOS	ENST00000526043.1	n.2444T>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 4	2
SELENOS	ENST00000526049.6	c.*581T>C		downstream_gene_variant		1	NM_018445.6	ENSP00000433541.1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112393 AN: 152152 Hom.: 42685 Cov.: 35

Gnomad AFR AF: 0.925

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.739 AC: 112500 AN: 152270 Hom.: 42736 Cov.: 35 AF XY: 0.734 AC XY: 54617 AN XY: 74444

Gnomad4 AFR AF: 0.925

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.746

Alfa AF: 0.692 Hom.: 50343

Bravo AF: 0.757

Asia WGS AF: 0.659 AC: 2292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.4
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs4965373; hg19: chr15-101812395;