chr8-142872956-C-T

Position:

chr8-142872956-C-T

Variant summary

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

The NM_000497.4(CYP11B1):c.*1417G>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 0.115 in 152,214 control chromosomes in the GnomAD database, including 1,342 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1341 hom., cov: 33)

Exomes 𝑓: 0.13 ( 1 hom. )

Consequence

CYP11B1
NM_000497.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.587

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=-0.96).

BP6

Variant 8-142872956-C-T is Benign according to our data. Variant chr8-142872956-C-T is described in ClinVar as [Benign]. Clinvar id is 362113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP11B1	NM_000497.4 linkuse as main transcript	c.*1417G>A		3_prime_UTR_variant	9/9	ENST00000292427.10
CYP11B1	NM_001026213.1 linkuse as main transcript	c.*1417G>A		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP11B1	ENST00000292427.10 linkuse as main transcript	c.*1417G>A	3_prime_UTR_variant	9/9	1	NM_000497.4	P1	P15538-1
CYP11B1	ENST00000519285.5 linkuse as main transcript	c.*1417G>A	3_prime_UTR_variant	4/4	1
GML	ENST00000522728.5 linkuse as main transcript	c.181+31731C>T	intron_variant		3
CYP11B1	ENST00000314111.4 linkuse as main transcript	n.3126G>A	non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17485

AN:

152072

Hom.:

1336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0660

Gnomad ASJ

AF:

0.0616

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0931

Gnomad FIN

AF:

0.0734

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.0849

Gnomad OTH

AF:

0.105

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

0.0625

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.115

AC:

17511

AN:

152190

Hom.:

1341

Cov.:

AF XY:

0.112

AC XY:

8346

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.215

Gnomad4 AMR

AF:

0.0659

Gnomad4 ASJ

AF:

0.0616

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0938

Gnomad4 FIN

AF:

0.0734

Gnomad4 NFE

AF:

0.0850

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.0974

Hom.:

152

Bravo

AF:

0.117

Asia WGS

AF:

0.0460

AC:

163

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

-0.96

CADD

Benign

3.8

DANN

Benign

0.27

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