15-101272190-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.556
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]

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ACMG classification

Classification made for transcript

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
SELENOSNM_203472.3 linkc.*14-545T>C intron_variant Intron 6 of 6 NP_982298.2
SELENOSNM_018445.6 linkc.*581T>C downstream_gene_variant ENST00000526049.6 NP_060915.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SELENOSENST00000398226.7 linkc.*8-545T>C intron_variant Intron 6 of 6 1 ENSP00000381282.3 Q9BQE4
SELENOSENST00000531964.5 linkc.*8-545T>C intron_variant Intron 6 of 6 3 ENSP00000433803.1 A0A182DWI4
SELENOSENST00000526043.1 linkn.2444T>C splice_region_variant, non_coding_transcript_exon_variant Exon 4 of 4 2
SELENOSENST00000526049.6 linkc.*581T>C downstream_gene_variant 1 NM_018445.6 ENSP00000433541.1 Q9BQE4

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4965373; hg19: chr15-101812395; API