rs104894071

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_000497.4(CYP11B1):​c.1103C>A​(p.Ala368Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

CYP11B1
NM_000497.4 missense

Scores

9
8
2

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.42
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.965
PP5
Variant 8-142875730-G-T is Pathogenic according to our data. Variant chr8-142875730-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 1187.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYP11B1NM_000497.4 linkuse as main transcriptc.1103C>A p.Ala368Asp missense_variant 6/9 ENST00000292427.10 NP_000488.3 P15538-1Q8TDD0
CYP11B1NM_001026213.1 linkuse as main transcriptc.1103C>A p.Ala368Asp missense_variant 6/8 NP_001021384.1 P15538-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYP11B1ENST00000292427.10 linkuse as main transcriptc.1103C>A p.Ala368Asp missense_variant 6/91 NM_000497.4 ENSP00000292427.5 P15538-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Deficiency of steroid 11-beta-monooxygenase Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJul 01, 2006- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.92
BayesDel_addAF
Pathogenic
0.47
D
BayesDel_noAF
Pathogenic
0.43
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T;D;.;.
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.87
D;D;T;T
M_CAP
Pathogenic
0.71
D
MetaRNN
Pathogenic
0.96
D;D;D;D
MetaSVM
Uncertain
0.57
D
MutationAssessor
Uncertain
2.8
.;M;M;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-4.8
D;D;D;D
REVEL
Pathogenic
0.67
Sift
Uncertain
0.021
D;D;D;D
Sift4G
Uncertain
0.0070
D;D;D;D
Polyphen
1.0, 1.0
.;D;.;D
Vest4
0.77, 0.83, 0.91
MutPred
0.83
.;.;.;Loss of ubiquitination at K441 (P = 0.0661);
MVP
0.95
MPC
0.57
ClinPred
1.0
D
GERP RS
4.4
Varity_R
1.0
gMVP
0.96

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.

Other links and lift over

dbSNP: rs104894071; hg19: chr8-143957146; API