Variant 6-32039119-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000500.9(CYP21A2):c.318G>C(p.Pro106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 1,483,998 control chromosomes in the GnomAD database, including 1,046 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P106P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.025 ( 141 hom., cov: 31)

Exomes 𝑓: 0.025 ( 905 hom. )

Consequence

CYP21A2
NM_000500.9 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.25

Variant links:

Genes affected

CYP21A2 (HGNC:2600): (cytochrome P450 family 21 subfamily A member 2) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone. Mutations in this gene cause congenital adrenal hyperplasia. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought to account for many cases of steroid 21-hydroxylase deficiency. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CYP21A2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 6-32039119-G-C is Benign according to our data. Variant chr6-32039119-G-C is described in ClinVar as [Benign]. Clinvar id is 256293.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-32039119-G-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.26 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0254 (3630/143174) while in subpopulation NFE AF= 0.0254 (1664/65546). AF 95% confidence interval is 0.0244. There are 141 homozygotes in gnomad4. There are 2105 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 141 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CYP21A2	NM_000500.9 linkuse as main transcript	c.318G>C	p.Pro106=	synonymous_variant	3/10	ENST00000644719.2
CYP21A2	NM_001128590.4 linkuse as main transcript	c.228G>C	p.Pro76=	synonymous_variant	2/9
CYP21A2	NM_001368143.2 linkuse as main transcript	c.-88G>C		5_prime_UTR_variant	3/10
CYP21A2	NM_001368144.2 linkuse as main transcript	c.-88G>C		5_prime_UTR_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP21A2	ENST00000644719.2 linkuse as main transcript	c.318G>C	p.Pro106=	synonymous_variant	3/10		NM_000500.9	P1

Frequencies

GnomAD3 genomes

AF:

0.0254

AC:

3629

AN:

143064

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.0850

Gnomad AMR

AF:

0.00865

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000689

Gnomad SAS

AF:

0.00957

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.00338

Gnomad NFE

AF:

0.0254

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.0229

AC:

5585

AN:

244218

Hom.:

211

AF XY:

0.0223

AC XY:

2936

AN XY:

131930

show subpopulations

Gnomad AFR exome

AF:

0.00316

Gnomad AMR exome

AF:

0.00474

Gnomad ASJ exome

AF:

0.000203

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00458

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.0219

Gnomad OTH exome

AF:

0.0175

GnomAD4 exome

AF:

0.0247

AC:

33124

AN:

1340824

Hom.:

905

Cov.:

AF XY:

0.0241

AC XY:

16010

AN XY:

665058

show subpopulations

Gnomad4 AFR exome

AF:

0.00311

Gnomad4 AMR exome

AF:

0.00519

Gnomad4 ASJ exome

AF:

0.000368

Gnomad4 EAS exome

AF:

0.000437

Gnomad4 SAS exome

AF:

0.00628

Gnomad4 FIN exome

AF:

0.155

Gnomad4 NFE exome

AF:

0.0238

Gnomad4 OTH exome

AF:

0.0182

GnomAD4 genome

AF:

0.0254

AC:

3630

AN:

143174

Hom.:

141

Cov.:

AF XY:

0.0304

AC XY:

2105

AN XY:

69312

show subpopulations

Gnomad4 AFR

AF:

0.00431

Gnomad4 AMR

AF:

0.00864

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000690

Gnomad4 SAS

AF:

0.00979

Gnomad4 FIN

AF:

0.171

Gnomad4 NFE

AF:

0.0254

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.00660

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.63

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over