rs34703687
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_005989.4(AKR1D1):c.477C>T(p.Asp159=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00258 in 1,614,066 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.014 ( 52 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 48 hom. )
Consequence
AKR1D1
NM_005989.4 synonymous
NM_005989.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.378
Genes affected
AKR1D1 (HGNC:388): (aldo-keto reductase family 1 member D1) The enzyme encoded by this gene is responsible for the catalysis of the 5-beta-reduction of bile acid intermediates and steroid hormones carrying a delta(4)-3-one structure. Deficiency of this enzyme may contribute to hepatic dysfunction. Three transcript variants encoding different isoforms have been found for this gene. Other variants may be present, but their full-length natures have not been determined yet. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
Variant 7-138105327-C-T is Benign according to our data. Variant chr7-138105327-C-T is described in ClinVar as [Benign]. Clinvar id is 259892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.378 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0139 (2112/152252) while in subpopulation AFR AF= 0.0483 (2005/41532). AF 95% confidence interval is 0.0465. There are 52 homozygotes in gnomad4. There are 974 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 52 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AKR1D1 | NM_005989.4 | c.477C>T | p.Asp159= | synonymous_variant | 5/9 | ENST00000242375.8 | |
AKR1D1 | NM_001190907.2 | c.477C>T | p.Asp159= | synonymous_variant | 5/8 | ||
AKR1D1 | XM_047420763.1 | c.309C>T | p.Asp103= | synonymous_variant | 4/8 | ||
AKR1D1 | NM_001190906.2 | c.457-1281C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AKR1D1 | ENST00000242375.8 | c.477C>T | p.Asp159= | synonymous_variant | 5/9 | 1 | NM_005989.4 | P1 | |
AKR1D1 | ENST00000432161.5 | c.477C>T | p.Asp159= | synonymous_variant | 5/8 | 2 | |||
AKR1D1 | ENST00000411726.6 | c.457-1281C>T | intron_variant | 2 | |||||
AKR1D1 | ENST00000468877.2 | n.387C>T | non_coding_transcript_exon_variant | 5/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0139 AC: 2108AN: 152134Hom.: 52 Cov.: 32
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GnomAD3 exomes AF: 0.00357 AC: 899AN: 251478Hom.: 22 AF XY: 0.00271 AC XY: 368AN XY: 135908
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GnomAD4 exome AF: 0.00140 AC: 2049AN: 1461814Hom.: 48 Cov.: 31 AF XY: 0.00124 AC XY: 899AN XY: 727210
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GnomAD4 genome ? AF: 0.0139 AC: 2112AN: 152252Hom.: 52 Cov.: 32 AF XY: 0.0131 AC XY: 974AN XY: 74428
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Congenital bile acid synthesis defect 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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