Variant 1-47143817-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001010969.4(CYP4A22):c.691T>C(p.Cys231Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,613,692 control chromosomes in the GnomAD database, including 138,199 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.42 ( 14837 hom., cov: 32)

Exomes 𝑓: 0.39 ( 123362 hom. )

Consequence

CYP4A22
NM_001010969.4 missense

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 0.733

Variant links:

Genes affected

CYP4A22 (HGNC:20575): (cytochrome P450 family 4 subfamily A member 22) 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 gene is part of a cluster of cytochrome P450 genes on chromosome 1p33. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

CYP4A22 links:

CYP4A22 (HGNC:):

CYP4A22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6936626E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4A22	NM_001010969.4 linkuse as main transcript	c.691T>C	p.Cys231Arg	missense_variant	6/12	ENST00000371891.8	NP_001010969.2	Q5TCH4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4A22	ENST00000371891.8 linkuse as main transcript	c.691T>C	p.Cys231Arg	missense_variant	6/12	1	NM_001010969.4	ENSP00000360958.3		Q5TCH4-1

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64190

AN:

151882

Hom.:

14813

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.934

Gnomad SAS

AF:

0.641

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.394

GnomAD3 exomes

AF:

0.452

AC:

113515

AN:

251200

Hom.:

29526

AF XY:

0.455

AC XY:

61735

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.494

Gnomad AMR exome

AF:

0.458

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.938

Gnomad SAS exome

AF:

0.633

Gnomad FIN exome

AF:

0.379

Gnomad NFE exome

AF:

0.352

Gnomad OTH exome

AF:

0.400

GnomAD4 exome

AF:

0.392

AC:

573637

AN:

1461692

Hom.:

123362

Cov.:

AF XY:

0.397

AC XY:

289011

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.506

Gnomad4 AMR exome

AF:

0.456

Gnomad4 ASJ exome

AF:

0.240

Gnomad4 EAS exome

AF:

0.941

Gnomad4 SAS exome

AF:

0.627

Gnomad4 FIN exome

AF:

0.374

Gnomad4 NFE exome

AF:

0.353

Gnomad4 OTH exome

AF:

0.409

GnomAD4 genome

AF:

0.423

AC:

64257

AN:

152000

Hom.:

14837

Cov.:

AF XY:

0.432

AC XY:

32105

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.495

Gnomad4 AMR

AF:

0.428

Gnomad4 ASJ

AF:

0.239

Gnomad4 EAS

AF:

0.934

Gnomad4 SAS

AF:

0.640

Gnomad4 FIN

AF:

0.365

Gnomad4 NFE

AF:

0.344

Gnomad4 OTH

AF:

0.400

Alfa

AF:

0.367

Hom.:

27081

Bravo

AF:

0.426

TwinsUK

AF:

0.368

AC:

1364

ALSPAC

AF:

0.354

AC:

1366

ESP6500AA

AF:

0.496

AC:

2187

ESP6500EA

AF:

0.338

AC:

2907

ExAC

AF:

0.454

AC:

55087

Asia WGS

AF:

0.744

AC:

2583

AN:

3478

EpiCase

AF:

0.344

EpiControl

AF:

0.346

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to

Other:1

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.6

DANN

Benign

0.23

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.071

T;T;T

MetaRNN

Benign

0.0000017

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-4.8

.;N;.

PrimateAI

Benign

0.39

PROVEAN

Benign

5.5

N;N;.

REVEL

Benign

0.14

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.023

MPC

0.35

ClinPred

0.0058

GERP RS

1.9

Varity_R

0.19

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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