chr10-4966996-T-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000380872.9(AKR1C1):āc.322T>Cā(p.Leu108=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,613,908 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.0057 ( 9 hom., cov: 33)
Exomes š: 0.0014 ( 15 hom. )
Consequence
AKR1C1
ENST00000380872.9 synonymous
ENST00000380872.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.690
Genes affected
AKR1C1 (HGNC:384): (aldo-keto reductase family 1 member C1) This gene encodes a member of the aldo/keto reductase superfamily, which consists of more than 40 known enzymes and proteins. These enzymes catalyze the conversion of aldehydes and ketones to their corresponding alcohols by utilizing NADH and/or NADPH as cofactors. The enzymes display overlapping but distinct substrate specificity. This enzyme catalyzes the reaction of progesterone to the inactive form 20-alpha-hydroxy-progesterone. This gene shares high sequence identity with three other gene members and is clustered with those three genes at chromosome 10p15-p14. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 10-4966996-T-C is Benign according to our data. Variant chr10-4966996-T-C is described in ClinVar as [Benign]. Clinvar id is 784081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.69 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00572 (871/152332) while in subpopulation AFR AF= 0.0169 (702/41568). AF 95% confidence interval is 0.0159. There are 9 homozygotes in gnomad4. There are 416 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AKR1C1 | NM_001353.6 | c.322T>C | p.Leu108= | synonymous_variant | 3/9 | ENST00000380872.9 | NP_001344.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AKR1C1 | ENST00000380872.9 | c.322T>C | p.Leu108= | synonymous_variant | 3/9 | 1 | NM_001353.6 | ENSP00000370254 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00572 AC: 870AN: 152214Hom.: 9 Cov.: 33
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GnomAD3 exomes AF: 0.00275 AC: 690AN: 251080Hom.: 7 AF XY: 0.00235 AC XY: 319AN XY: 135690
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GnomAD4 exome AF: 0.00139 AC: 2035AN: 1461576Hom.: 15 Cov.: 30 AF XY: 0.00133 AC XY: 969AN XY: 727078
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GnomAD4 genome AF: 0.00572 AC: 871AN: 152332Hom.: 9 Cov.: 33 AF XY: 0.00558 AC XY: 416AN XY: 74508
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 26, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at