rs4965814

Variant names:

• chr15-101273712-C-T
• rs4965814
• NM_018445.6:c.484+708G>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.484+708G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,068 control chromosomes in the GnomAD database, including 35,236 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 0.63 (35236 hom., cov: 32)
• Consequence: SELENOS NM_018445.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 23 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.855 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.484+708G>A		intron	N/A	NP_060915.2
	SELENOS	NM_203472.3		c.484+708G>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.484+708G>A		intron	N/A	ENSP00000433541.1	Q9BQE4
	SELENOS	ENST00000398226.8	TSL:1	c.484+708G>A		intron	N/A	ENSP00000381282.3	Q9BQE4
	SELENOS	ENST00000528346.1	TSL:3	c.604+708G>A		intron	N/A	ENSP00000434842.1	E9PN30

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95859 AN: 151950 Hom.: 35244 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.630 AC: 95861 AN: 152068 Hom.: 35236 Cov.: 32 AF XY: 0.631 AC XY: 46913 AN XY: 74346

African (AFR) AF: 0.231 AC: 9596 AN: 41462

American (AMR) AF: 0.649 AC: 9924 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2851 AN: 3470

East Asian (EAS) AF: 0.583 AC: 3010 AN: 5160

South Asian (SAS) AF: 0.877 AC: 4238 AN: 4830

European-Finnish (FIN) AF: 0.743 AC: 7852 AN: 10570

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55896 AN: 67980

Other (OTH) AF: 0.665 AC: 1404 AN: 2112

Alfa AF: 0.757 Hom.: 40956

Bravo AF: 0.599

Asia WGS AF: 0.728 AC: 2534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.76
PhyloP100		-0.62
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: rs4965814; hg19: chr15-101813917;