chr15-101276024-C-T

Variant names:

• chr15-101276024-C-T
• rs2009895
• NM_018445.6:c.211+517G>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.211+517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 150,756 control chromosomes in the GnomAD database, including 341 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 0.034 (341 hom., cov: 30)
• Consequence: SELENOS NM_018445.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.231 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.211+517G>A		intron	N/A	NP_060915.2
	SELENOS	NM_203472.3		c.211+517G>A		intron	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.211+517G>A		intron	N/A	ENSP00000433541.1	Q9BQE4
	SELENOS	ENST00000398226.8	TSL:1	c.211+517G>A		intron	N/A	ENSP00000381282.3	Q9BQE4
	SELENOS	ENST00000528346.1	TSL:3	c.331+517G>A		intron	N/A	ENSP00000434842.1	E9PN30

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5098 AN: 150654 Hom.: 336 Cov.: 30

Gnomad AFR AF: 0.00999

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.00722

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.0230

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.0221

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

GnomAD4 genome AF: 0.0339 AC: 5110 AN: 150756 Hom.: 341 Cov.: 30 AF XY: 0.0381 AC XY: 2805 AN XY: 73576

African (AFR) AF: 0.00998 AC: 409 AN: 40966

American (AMR) AF: 0.130 AC: 1971 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.00722 AC: 25 AN: 3464

East Asian (EAS) AF: 0.242 AC: 1226 AN: 5062

South Asian (SAS) AF: 0.0337 AC: 160 AN: 4754

European-Finnish (FIN) AF: 0.0398 AC: 409 AN: 10264

Middle Eastern (MID) AF: 0.0211 AC: 6 AN: 284

European-Non Finnish (NFE) AF: 0.0126 AC: 856 AN: 67810

Other (OTH) AF: 0.0219 AC: 46 AN: 2098

Alfa AF: 0.0196 Hom.: 15

Bravo AF: 0.0431

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.81
DANN	Benign	0.58
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2009895; hg19: chr15-101816229;