8-64596593-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004820.5(CYP7B1):c.*49C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,517,454 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 35 hom. )

Consequence

CYP7B1
NM_004820.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.741

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 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=-0.83).

BP6

Variant 8-64596593-G-A is Benign according to our data. Variant chr8-64596593-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 908301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.002 (304/152266) while in subpopulation EAS AF= 0.0226 (117/5188). AF 95% confidence interval is 0.0192. There are 4 homozygotes in gnomad4. There are 194 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CYP7B1	NM_004820.5 link	c.*49C>T	3_prime_UTR_variant	Exon 6 of 6	ENST00000310193.4	NP_004811.1	O75881Q05C57
CYP7B1	XM_017014002.2 link	c.*49C>T	3_prime_UTR_variant	Exon 7 of 7		XP_016869491.1
CYP7B1	NM_001324112.2 link	c.1234-6749C>T	intron_variant	Intron 5 of 6		NP_001311041.1	Q05C57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP7B1	ENST00000310193 link	c.*49C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_004820.5	ENSP00000310721.3		O75881
CYP7B1	ENST00000523954.1 link	n.508-6749C>T		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes

AF:

0.00201

AC:

306

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00491

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0229

Gnomad SAS

AF:

0.0182

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00556

AC:

1124

AN:

202322

Hom.:

AF XY:

0.00568

AC XY:

623

AN XY:

109728

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0155

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0164

Gnomad SAS exome

AF:

0.0148

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000710

Gnomad OTH exome

AF:

0.00192

GnomAD4 exome

AF:

0.00191

AC:

2603

AN:

1365188

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

1535

AN XY:

680628

show subpopulations

Gnomad4 AFR exome

AF:

0.0000976

Gnomad4 AMR exome

AF:

0.0136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0185

Gnomad4 SAS exome

AF:

0.0145

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000713

Gnomad4 OTH exome

AF:

0.00180

GnomAD4 genome

AF:

0.00200

AC:

304

AN:

152266

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

194

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00491

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0226

Gnomad4 SAS

AF:

0.0182

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000952

Hom.:

Bravo

AF:

0.00227

Asia WGS

AF:

0.0140

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 09, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hereditary spastic paraplegia 5A

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.86

DANN

Benign

0.41

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.

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