dbSNP rs10808739: CYP7B1:c.122+70763C>T (chr8-64727703-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004820.5(CYP7B1):c.122+70763C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 151,952 control chromosomes in the GnomAD database, including 4,641 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4641 hom., cov: 32)

Consequence

CYP7B1
NM_004820.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.793

Publications

16 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:

ENSG00000254330 (HGNC:):

ENSG00000254330 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP7B1	NM_004820.5 link	c.122+70763C>T		intron_variant	Intron 1 of 5	ENST00000310193.4	NP_004811.1	O75881Q05C57
CYP7B1	NM_001324112.2 link	c.122+70763C>T		intron_variant	Intron 1 of 6		NP_001311041.1	Q05C57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP7B1	ENST00000310193.4 link	c.122+70763C>T		intron_variant	Intron 1 of 5	1	NM_004820.5	ENSP00000310721.3		O75881
ENSG00000254330	ENST00000519680.1 link	n.509+251C>T		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35450

AN:

151832

Hom.:

4644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.345

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.0288

Gnomad SAS

AF:

0.182

Gnomad FIN

AF:

0.154

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.227

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.233

AC:

35455

AN:

151952

Hom.:

4641

Cov.:

AF XY:

0.229

AC XY:

16978

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.345

AC:

14276

AN:

41422

American (AMR)

AF:

0.192

AC:

2930

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

646

AN:

3464

East Asian (EAS)

AF:

0.0289

AC:

149

AN:

5164

South Asian (SAS)

AF:

0.181

AC:

869

AN:

4806

European-Finnish (FIN)

AF:

0.154

AC:

1622

AN:

10562

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14269

AN:

67940

Other (OTH)

AF:

0.225

AC:

474

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1375

2749

4124

5498

6873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.214

Hom.:

15046

Bravo

AF:

0.238

Asia WGS

AF:

0.102

AC:

358

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

(source)

DANN

Benign

0.77

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over