Variant 6-32041507-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000500.9(CYP21A2):c.*373G>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 0.0201 in 1,215,108 control chromosomes in the GnomAD database, including 2,328 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.054 ( 786 hom., cov: 24)

Exomes 𝑓: 0.015 ( 1542 hom. )

Consequence

CYP21A2
NM_000500.9 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.87

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:

TNXB (HGNC:11976): (tenascin XB) This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The tenascins have anti-adhesive effects, as opposed to fibronectin which is adhesive. This protein is thought to function in matrix maturation during wound healing, and its deficiency has been associated with the connective tissue disorder Ehlers-Danlos syndrome. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. It is one of four genes in this cluster which have been duplicated. The duplicated copy of this gene is incomplete and is a pseudogene which is transcribed but does not encode a protein. The structure of this gene is unusual in that it overlaps the CREBL1 and CYP21A2 genes at its 5' and 3' ends, respectively. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TNXB links:

TNXB (HGNC:):

TNXB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

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

BP6

Variant 6-32041507-G-A is Benign according to our data. Variant chr6-32041507-G-A is described in ClinVar as [Benign]. Clinvar id is 1264810.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP21A2	NM_000500.9 linkuse as main transcript	c.*373G>A		3_prime_UTR_variant	10/10	ENST00000644719.2	NP_000491.4	P08686Q16874Q08AG9
TNXB	NM_001365276.2 linkuse as main transcript	c.12634-57C>T		intron_variant		ENST00000644971.2	NP_001352205.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP21A2	ENST00000644719.2 linkuse as main transcript	c.*373G>A		3_prime_UTR_variant	10/10		NM_000500.9	ENSP00000496625.1		Q16874
TNXB	ENST00000644971.2 linkuse as main transcript	c.12634-57C>T		intron_variant			NM_001365276.2	ENSP00000496448.1		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0544

AC:

7840

AN:

144206

Hom.:

785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.0306

Gnomad AMR

AF:

0.0517

Gnomad ASJ

AF:

0.0157

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00210

Gnomad FIN

AF:

0.00261

Gnomad MID

AF:

0.0362

Gnomad NFE

AF:

0.0422

Gnomad OTH

AF:

0.0540

GnomAD4 exome

AF:

0.0155

AC:

16546

AN:

1070774

Hom.:

1542

Cov.:

AF XY:

0.0149

AC XY:

8071

AN XY:

540436

show subpopulations

Gnomad4 AFR exome

AF:

0.0668

Gnomad4 AMR exome

AF:

0.0267

Gnomad4 ASJ exome

AF:

0.00978

Gnomad4 EAS exome

AF:

0.0000289

Gnomad4 SAS exome

AF:

0.000775

Gnomad4 FIN exome

AF:

0.00418

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0238

GnomAD4 genome

AF:

0.0544

AC:

7848

AN:

144334

Hom.:

786

Cov.:

AF XY:

0.0512

AC XY:

3601

AN XY:

70386

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.0517

Gnomad4 ASJ

AF:

0.0157

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00261

Gnomad4 NFE

AF:

0.0422

Gnomad4 OTH

AF:

0.0534

Alfa

AF:

0.00817

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.35

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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