Variant 1-47142179-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001010969.4(CYP4A22):c.454A>T(p.Asn152Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 1,613,266 control chromosomes in the GnomAD database, including 187,716 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 Lovd as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.56 ( 27783 hom., cov: 31)

Exomes 𝑓: 0.45 ( 159933 hom. )

Consequence

CYP4A22
NM_001010969.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.18

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-AS1 (HGNC:43715): (CYP4A22 antisense RNA 1)

CYP4A22-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.5095486E-6).

BP6

Variant 1-47142179-A-T is Benign according to our data. Variant chr1-47142179-A-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4A22	NM_001010969.4 linkuse as main transcript	c.454A>T	p.Asn152Tyr	missense_variant	4/12	ENST00000371891.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4A22	ENST00000371891.8 linkuse as main transcript	c.454A>T	p.Asn152Tyr	missense_variant	4/12	1	NM_001010969.4	P1	Q5TCH4-1
CYP4A22-AS1	ENST00000444042.2 linkuse as main transcript	n.396+34856T>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.562

AC:

85291

AN:

151800

Hom.:

27721

Cov.:

show subpopulations

Gnomad AFR

AF:

0.862

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.498

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.681

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.500

GnomAD3 exomes

AF:

0.521

AC:

130675

AN:

250796

Hom.:

38827

AF XY:

0.518

AC XY:

70174

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.870

Gnomad AMR exome

AF:

0.499

Gnomad ASJ exome

AF:

0.307

Gnomad EAS exome

AF:

0.981

Gnomad SAS exome

AF:

0.679

Gnomad FIN exome

AF:

0.442

Gnomad NFE exome

AF:

0.398

Gnomad OTH exome

AF:

0.461

GnomAD4 exome

AF:

0.447

AC:

652884

AN:

1461346

Hom.:

159933

Cov.:

AF XY:

0.451

AC XY:

327570

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.884

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.307

Gnomad4 EAS exome

AF:

0.990

Gnomad4 SAS exome

AF:

0.673

Gnomad4 FIN exome

AF:

0.433

Gnomad4 NFE exome

AF:

0.397

Gnomad4 OTH exome

AF:

0.477

GnomAD4 genome

AF:

0.562

AC:

85416

AN:

151920

Hom.:

27783

Cov.:

AF XY:

0.570

AC XY:

42318

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.862

Gnomad4 AMR

AF:

0.498

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.979

Gnomad4 SAS

AF:

0.680

Gnomad4 FIN

AF:

0.432

Gnomad4 NFE

AF:

0.390

Gnomad4 OTH

AF:

0.505

Alfa

AF:

0.420

Hom.:

4811

Bravo

AF:

0.576

TwinsUK

AF:

0.409

AC:

1516

ALSPAC

AF:

0.397

AC:

1531

ESP6500AA

AF:

0.848

AC:

3737

ESP6500EA

AF:

0.387

AC:

3324

ExAC

AF:

0.530

AC:

64297

EpiCase

AF:

0.394

EpiControl

AF:

0.395

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.0

DANN

Benign

0.82

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.033

T;T;T;T;T

MetaRNN

Benign

0.0000015

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.51

PROVEAN

Benign

6.6

N;.;N;N;.

REVEL

Benign

0.13

Sift

Benign

1.0

T;.;T;T;.

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;.;.;B;.

Vest4

0.079

MPC

0.072

ClinPred

0.0050

GERP RS

0.25

Varity_R

0.044

gMVP

0.25

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over