Genetic Variant CYP7B1:p.Pro20Arg (chr8-64798529-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004820.5(CYP7B1):c.59C>G(p.Pro20Arg) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P20L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CYP7B1
NM_004820.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0420

Publications

0 publications found

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]

CYP7B1 Gene-Disease associations (from GenCC):

congenital bile acid synthesis defect 3
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
hereditary spastic paraplegia 5A
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

CYP7B1 links:

ENSG00000287998 (HGNC:):

ENSG00000287998 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10424158).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004820.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP7B1	NM_004820.5	MANE Select	c.59C>G	p.Pro20Arg	missense	Exon 1 of 6	NP_004811.1
	CYP7B1	NM_001324112.2		c.59C>G	p.Pro20Arg	missense	Exon 1 of 7	NP_001311041.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CYP7B1	ENST00000310193.4	TSL:1 MANE Select	c.59C>G	p.Pro20Arg	missense	Exon 1 of 6	ENSP00000310721.3
ENSG00000287998	ENST00000833571.1		n.66G>C		non_coding_transcript_exon	Exon 1 of 2
ENSG00000287998	ENST00000833563.1		n.-85G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1349052

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

665468

African (AFR)

AF:

0.00

AC:

AN:

27306

American (AMR)

AF:

0.00

AC:

AN:

31276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23958

East Asian (EAS)

AF:

0.00

AC:

AN:

31324

South Asian (SAS)

AF:

0.00

AC:

AN:

75684

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3970

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1066056

Other (OTH)

AF:

0.00

AC:

AN:

56172

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000383

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.9

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.23

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.43

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

-0.042

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.1

REVEL

Benign

0.14

Sift

Benign

0.13

Sift4G

Benign

0.35

Polyphen

0.032

Vest4

0.27

MutPred

0.51

Gain of methylation at P20 (P = 0.0024)

MVP

0.54

MPC

0.088

ClinPred

0.049

GERP RS

-2.2

PromoterAI

-0.011

Neutral

(source)

Varity_R

0.035

gMVP

0.54

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over