6-32041147-G-A
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_000500.9(CYP21A2):c.*13G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,587,566 control chromosomes in the GnomAD database, including 685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000500.9 3_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0157 AC: 2380AN: 151294Hom.: 58 Cov.: 33
GnomAD3 exomes AF: 0.0253 AC: 5997AN: 236776Hom.: 131 AF XY: 0.0233 AC XY: 3028AN XY: 129706
GnomAD4 exome AF: 0.0173 AC: 24837AN: 1436150Hom.: 627 Cov.: 33 AF XY: 0.0171 AC XY: 12261AN XY: 714970
GnomAD4 genome AF: 0.0157 AC: 2378AN: 151416Hom.: 58 Cov.: 33 AF XY: 0.0160 AC XY: 1186AN XY: 73984
ClinVar
Submissions by phenotype
Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency Pathogenic:2Uncertain:1Benign:1
PM3_VeryStrong+PP4 -
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not provided Uncertain:1Benign:1
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Available data are insufficient to determine the clinical significance of the variant at this time. This variant is located in a genomic region of low or unreliable sequencing quality, and therefore estimations of its population frequency are uninformative in assessment of variant pathogenicity. This variant has been seen in trans with other recessive pathogenic CYP21A2 variants in multiple individuals with classic and also nonclassic forms of CAH. Assessment of experimental evidence regarding the effect of this variant on protein function is inconclusive. Results from PMID: 21521936 show a reduction in mRNA levels due to this variant, however, neither protein levels nor protein activity were assayed. This variant is also referred to by nucleotide 4397 in some published literature, and has been previously reported by Athena Diagnostics at nucleotide 1501. -
CYP21A2-related disorder Uncertain:1
The CYP21A2 c.*13G>A variant is located in the 3' untranslated region. This particular variant has been previously reported to be associated with a mild form of congenital adrenal hyperplasia (CAH) (Menabò et al. 2012. PubMed ID: 21521936). Its minor allele frequency is up to ~7.5% in East Asian individuals. However, this minor allele frequency is based on the current next-generation sequencing technology and may not be an accurate estimate because this variant is located within a highly homologous sequence region (Mandelker et al. 2016. PubMed ID: 27228465). Due to limited functional and genetic evidence, the clinical significance of the c.*13G>A variant is currently uncertain. -
not specified Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at