5-42806886-A-G
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005410.4(SELENOP):c.416+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,512,442 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.012 ( 35 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 37 hom. )
Consequence
SELENOP
NM_005410.4 intron
NM_005410.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0900
Genes affected
SELENOP (HGNC:10751): (selenoprotein P) This gene encodes a selenoprotein that is predominantly expressed in the liver and secreted into the plasma. This selenoprotein is unique in that it contains multiple selenocysteine (Sec) residues per polypeptide (10 in human), and accounts for most of the selenium in plasma. It has been implicated as an extracellular antioxidant, and in the transport of selenium to extra-hepatic tissues via apolipoprotein E receptor-2 (apoER2). Mice lacking this gene exhibit neurological dysfunction, suggesting its importance in normal brain function. 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. The mRNA for this selenoprotein contains two SECIS elements. The use of alternative polyadenylation sites, one located in between the two SECIS elements, results in two populations of mRNAs containing either both (predominant) or just the upstream SECIS element (PMID:27881738). Alternatively spliced transcript variants have also been found for this gene. [provided by RefSeq, Oct 2018]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 5-42806886-A-G is Benign according to our data. Variant chr5-42806886-A-G is described in ClinVar as [Benign]. Clinvar id is 787815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0124 (1885/152280) while in subpopulation AFR AF = 0.0432 (1794/41568). AF 95% confidence interval is 0.0415. There are 35 homozygotes in GnomAd4. There are 845 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
BS2
High Homozygotes in GnomAd4 at 35 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SELENOP | NM_005410.4 | c.416+10T>C | intron_variant | Intron 3 of 4 | ENST00000514985.6 | NP_005401.3 | ||
SELENOP | NM_001093726.3 | c.506+10T>C | intron_variant | Intron 4 of 5 | NP_001087195.1 | |||
SELENOP | NM_001085486.3 | c.416+10T>C | intron_variant | Intron 4 of 5 | NP_001078955.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0123 AC: 1878AN: 152162Hom.: 35 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1878
AN:
152162
Hom.:
Cov.:
32
Gnomad AFR
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GnomAD2 exomes AF: 0.00328 AC: 794AN: 241862 AF XY: 0.00240 show subpopulations
GnomAD2 exomes
AF:
AC:
794
AN:
241862
AF XY:
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GnomAD4 exome AF: 0.00118 AC: 1609AN: 1360162Hom.: 37 Cov.: 20 AF XY: 0.00106 AC XY: 721AN XY: 677616 show subpopulations
GnomAD4 exome
AF:
AC:
1609
AN:
1360162
Hom.:
Cov.:
20
AF XY:
AC XY:
721
AN XY:
677616
Gnomad4 AFR exome
AF:
AC:
1352
AN:
31060
Gnomad4 AMR exome
AF:
AC:
77
AN:
41948
Gnomad4 ASJ exome
AF:
AC:
0
AN:
24894
Gnomad4 EAS exome
AF:
AC:
0
AN:
38746
Gnomad4 SAS exome
AF:
AC:
12
AN:
81250
Gnomad4 FIN exome
AF:
AC:
0
AN:
52510
Gnomad4 NFE exome
AF:
AC:
30
AN:
1027820
Gnomad4 Remaining exome
AF:
AC:
134
AN:
56556
Heterozygous variant carriers
0
71
142
214
285
356
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
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Age
GnomAD4 genome AF: 0.0124 AC: 1885AN: 152280Hom.: 35 Cov.: 32 AF XY: 0.0113 AC XY: 845AN XY: 74458 show subpopulations
GnomAD4 genome
AF:
AC:
1885
AN:
152280
Hom.:
Cov.:
32
AF XY:
AC XY:
845
AN XY:
74458
Gnomad4 AFR
AF:
AC:
0.0431582
AN:
0.0431582
Gnomad4 AMR
AF:
AC:
0.00457875
AN:
0.00457875
Gnomad4 ASJ
AF:
AC:
0
AN:
0
Gnomad4 EAS
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AC:
0
AN:
0
Gnomad4 SAS
AF:
AC:
0.000207211
AN:
0.000207211
Gnomad4 FIN
AF:
AC:
0
AN:
0
Gnomad4 NFE
AF:
AC:
0.0000441151
AN:
0.0000441151
Gnomad4 OTH
AF:
AC:
0.00804163
AN:
0.00804163
Heterozygous variant carriers
0
92
184
275
367
459
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
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66
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Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
5
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Mar 30, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Mutation Taster
=100/0
polymorphism
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at