dbSNP rs28628459: SELENOS:c.*8-507A>G (chr15-101272152-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000398226.8(SELENOS):c.*8-507A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,232 control chromosomes in the GnomAD database, including 7,081 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 ( 7081 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

SELENOS
ENST00000398226.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.523

Publications

7 publications found

Variant links:

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]

SELENOS links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOS	NM_203472.3 link	c.*14-507A>G		intron_variant	Intron 6 of 6		NP_982298.2
SELENOS	NM_018445.6 link	c.*619A>G		downstream_gene_variant		ENST00000526049.6	NP_060915.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SELENOS	ENST00000398226.8 link	c.*8-507A>G	intron_variant	Intron 6 of 6	1		ENSP00000381282.3	Q9BQE4
SELENOS	ENST00000531964.5 link	c.*8-507A>G	intron_variant	Intron 6 of 6	3		ENSP00000433803.1	A0A182DWI4
SELENOS	ENST00000526049.6 link	c.*619A>G	downstream_gene_variant		1	NM_018445.6	ENSP00000433541.1	Q9BQE4
SELENOS	ENST00000526043.1 link	n.*38A>G	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37157

AN:

152114

Hom.:

7070

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.0179

Gnomad SAS

AF:

0.0654

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.207

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.244

AC:

37204

AN:

152232

Hom.:

7081

Cov.:

AF XY:

0.240

AC XY:

17844

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.534

AC:

22169

AN:

41506

American (AMR)

AF:

0.143

AC:

2181

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

557

AN:

3472

East Asian (EAS)

AF:

0.0175

AC:

AN:

5192

South Asian (SAS)

AF:

0.0654

AC:

316

AN:

4830

European-Finnish (FIN)

AF:

0.182

AC:

1931

AN:

10592

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.138

AC:

9418

AN:

68024

Other (OTH)

AF:

0.212

AC:

448

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1215

2431

3646

4862

6077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.212

Hom.:

681

Bravo

AF:

0.258

Asia WGS

AF:

0.0850

AC:

295

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.40

PhyloP100

-0.52

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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rs28628459

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over