rs112066175

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004391.3(CYP8B1):c.1204G>A(p.Val402Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00841 in 1,614,040 control chromosomes in the GnomAD database, including 77 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0067 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 73 hom. )

Consequence

CYP8B1
NM_004391.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.873

Variant links:

Genes affected

CYP8B1 (HGNC:2653): (cytochrome P450 family 8 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 conversion of 7 alpha-hydroxy-4-cholesten-3-one into 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one. The balance between these two steroids determines the relative amounts of cholic acid and chenodeoxycholic acid both of which are secreted in the bile and affect the solubility of cholesterol. This gene is unique among the cytochrome P450 genes in that it is intronless. [provided by RefSeq, Jul 2008]

CYP8B1 links:

ENSG00000290317 (HGNC:):

ENSG00000290317 links:

ACKR2 (HGNC:1565): (atypical chemokine receptor 2) This gene encodes a beta chemokine receptor, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. Chemokines and their receptor-mediated signal transduction are critical for the recruitment of effector immune cells to the inflammation site. This gene is expressed in a range of tissues and hemopoietic cells. The expression of this receptor in lymphatic endothelial cells and overexpression in vascular tumors suggested its function in chemokine-driven recirculation of leukocytes and possible chemokine effects on the development and growth of vascular tumors. This receptor appears to bind the majority of beta-chemokine family members; however, its specific function remains unknown. This gene is mapped to chromosome 3p21.3, a region that includes a cluster of chemokine receptor genes. [provided by RefSeq, Jul 2008]

ACKR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011722803).

BP6

Variant 3-42874613-C-T is Benign according to our data. Variant chr3-42874613-C-T is described in ClinVar as [Benign]. Clinvar id is 769272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP8B1	NM_004391.3 link	c.1204G>A	p.Val402Ile	missense_variant	Exon 1 of 1	ENST00000316161.6	NP_004382.2	Q9UNU6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP8B1	ENST00000316161.6 link	c.1204G>A	p.Val402Ile	missense_variant	Exon 1 of 1	6	NM_004391.3	ENSP00000318867.4		Q9UNU6
ENSG00000290317	ENST00000426937.5 link	c.-163-34180C>T		intron_variant	Intron 2 of 6	3		ENSP00000413859.1

Frequencies

GnomAD3 genomes

AF:

0.00672

AC:

1022

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.0154

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00965

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00592

AC:

1488

AN:

251486

Hom.:

AF XY:

0.00578

AC XY:

786

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00228

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.00889

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00859

AC:

12557

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00840

AC XY:

6109

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.0139

Gnomad4 NFE exome

AF:

0.0100

Gnomad4 OTH exome

AF:

0.00704

GnomAD4 genome

AF:

0.00671

AC:

1021

AN:

152150

Hom.:

Cov.:

AF XY:

0.00698

AC XY:

519

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00181

Gnomad4 AMR

AF:

0.00687

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000624

Gnomad4 FIN

AF:

0.0154

Gnomad4 NFE

AF:

0.00963

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00799

Hom.:

Bravo

AF:

0.00541

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00872

AC:

ExAC

AF:

0.00586

AC:

712

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00752

EpiControl

AF:

0.00771

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 28, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.14

DANN

Benign

0.77

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.44

T;T

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

.;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.68

N;N

REVEL

Benign

0.034

Sift

Benign

0.21

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.012

B;B

Vest4

0.058

MVP

0.014

MPC

0.089

ClinPred

0.0032

GERP RS

-7.0

Varity_R

0.026

gMVP

0.39

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