rs368975126
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001206979.2(NR1H4):c.1245T>C(p.Leu415=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000142 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
NR1H4
NM_001206979.2 synonymous
NM_001206979.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.73
Genes affected
NR1H4 (HGNC:7967): (nuclear receptor subfamily 1 group H member 4) This gene encodes a ligand-activated transcription factor that shares structural features in common with nuclear hormone receptor family members. This protein functions as a receptor for bile acids, and when bound to bile acids, binds to DNA and regulates the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 12-100563303-T-C is Benign according to our data. Variant chr12-100563303-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 259642.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR1H4 | NM_001206979.2 | c.1245T>C | p.Leu415= | synonymous_variant | 11/11 | ENST00000392986.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR1H4 | ENST00000392986.8 | c.1245T>C | p.Leu415= | synonymous_variant | 11/11 | 1 | NM_001206979.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152196Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727246
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GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74346
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 07, 2016 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
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Dann
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at