8-142872807-C-A

Position:

chr8-142872807-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000497.4(CYP11B1):c.*1566G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,042 control chromosomes in the GnomAD database, including 29,006 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 29003 hom., cov: 32)

Exomes 𝑓: 0.64 ( 3 hom. )

Consequence

CYP11B1
NM_000497.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.118

Variant links:

Genes affected

CYP11B1 (HGNC:2591): (cytochrome P450 family 11 subfamily B member 1) 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 mitochondrial inner membrane and is involved in the conversion of progesterone to cortisol in the adrenal cortex. Mutations in this gene cause congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. Transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

CYP11B1 links:

GML (HGNC:4375): (glycosylphosphatidylinositol anchored molecule like) Predicted to be involved in DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; apoptotic process; and negative regulation of cell population proliferation. Predicted to be extrinsic component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

GML links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 8-142872807-C-A is Benign according to our data. Variant chr8-142872807-C-A is described in ClinVar as [Benign]. Clinvar id is 362108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP11B1	NM_000497.4 linkuse as main transcript	c.*1566G>T		3_prime_UTR_variant	9/9	ENST00000292427.10	NP_000488.3
CYP11B1	NM_001026213.1 linkuse as main transcript	c.*1566G>T		3_prime_UTR_variant	8/8		NP_001021384.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP11B1	ENST00000292427.10 linkuse as main transcript	c.*1566G>T	3_prime_UTR_variant	9/9	1	NM_000497.4	ENSP00000292427	P1	P15538-1
CYP11B1	ENST00000519285.5 linkuse as main transcript	c.*1566G>T	3_prime_UTR_variant	4/4	1		ENSP00000430144
GML	ENST00000522728.5 linkuse as main transcript	c.181+31582C>A	intron_variant		3		ENSP00000430799
CYP11B1	ENST00000314111.4 linkuse as main transcript	n.3275G>T	non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93367

AN:

151908

Hom.:

28983

Cov.:

show subpopulations

Gnomad AFR

AF:

0.640

Gnomad AMI

AF:

0.559

Gnomad AMR

AF:

0.636

Gnomad ASJ

AF:

0.647

Gnomad EAS

AF:

0.848

Gnomad SAS

AF:

0.738

Gnomad FIN

AF:

0.613

Gnomad MID

AF:

0.656

Gnomad NFE

AF:

0.566

Gnomad OTH

AF:

0.630

GnomAD4 exome

AF:

0.643

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.750

Gnomad4 NFE exome

AF:

0.625

GnomAD4 genome

AF:

0.615

AC:

93437

AN:

152028

Hom.:

29003

Cov.:

AF XY:

0.623

AC XY:

46273

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.640

Gnomad4 AMR

AF:

0.637

Gnomad4 ASJ

AF:

0.647

Gnomad4 EAS

AF:

0.847

Gnomad4 SAS

AF:

0.740

Gnomad4 FIN

AF:

0.613

Gnomad4 NFE

AF:

0.566

Gnomad4 OTH

AF:

0.626

Alfa

AF:

0.580

Hom.:

51873

Bravo

AF:

0.613

Asia WGS

AF:

0.729

AC:

2535

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Deficiency of steroid 11-beta-monooxygenase

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Glucocorticoid-remediable aldosteronism

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.84

DANN

Benign

0.45

Splicing

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