8-64596702-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004820.5(CYP7B1):​c.1461G>T​(p.Leu487Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CYP7B1
NM_004820.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.809
Variant links:
Genes affected
CYP7B1 (HGNC:2652): (cytochrome P450 family 7 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 endoplasmic reticulum membrane protein catalyzes the first reaction in the cholesterol catabolic pathway of extrahepatic tissues, which converts cholesterol to bile acids. This enzyme likely plays a minor role in total bile acid synthesis, but may also be involved in the development of atherosclerosis, neurosteroid metabolism and sex hormone synthesis. Mutations in this gene have been associated with hereditary spastic paraplegia (SPG5 or HSP), an autosomal recessive disorder. [provided by RefSeq, Apr 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11553794).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYP7B1NM_004820.5 linkc.1461G>T p.Leu487Phe missense_variant Exon 6 of 6 ENST00000310193.4 NP_004811.1 O75881Q05C57
CYP7B1XM_017014002.2 linkc.1527G>T p.Leu509Phe missense_variant Exon 7 of 7 XP_016869491.1
CYP7B1NM_001324112.2 linkc.1234-6858G>T intron_variant Intron 5 of 6 NP_001311041.1 Q05C57

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYP7B1ENST00000310193.4 linkc.1461G>T p.Leu487Phe missense_variant Exon 6 of 6 1 NM_004820.5 ENSP00000310721.3 O75881
CYP7B1ENST00000523954.1 linkn.508-6858G>T intron_variant Intron 3 of 4 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
May 11, 2018
Eurofins Ntd Llc (ga)
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
0.60
DANN
Benign
0.94
DEOGEN2
Benign
0.13
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.057
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.84
T
MutationAssessor
Benign
0.29
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.12
Sift
Benign
0.18
T
Sift4G
Benign
0.33
T
Polyphen
0.0060
B
Vest4
0.025
MutPred
0.52
Loss of stability (P = 0.0515);
MVP
0.65
MPC
0.084
ClinPred
0.044
T
GERP RS
1.3
Varity_R
0.034
gMVP
0.61

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: rs1213447459; hg19: chr8-65509259; API