1-47142179-A-T

Variant names:

• chr1-47142179-A-T
• rs2056899
• NM_001010969.4:c.454A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (27783 hom., cov: 31)
  • Exomes 𝑓: 0.45 (159933 hom.)
• Consequence: CYP4A22 NM_001010969.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18
• Publications: 29 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.5095486E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010969.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4A22	NM_001010969.4	MANE Select	c.454A>T	p.Asn152Tyr	missense	Exon 4 of 12	NP_001010969.2
	CYP4A22	NM_001437457.1		c.454A>T	p.Asn152Tyr	missense	Exon 4 of 10	NP_001424386.1
	CYP4A22	NM_001308102.2		c.454A>T	p.Asn152Tyr	missense	Exon 4 of 9	NP_001295031.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4A22	ENST00000371891.8	TSL:1 MANE Select	c.454A>T	p.Asn152Tyr	missense	Exon 4 of 12	ENSP00000360958.3
	CYP4A22	ENST00000294337.7	TSL:1	c.454A>T	p.Asn152Tyr	missense	Exon 4 of 11	ENSP00000294337.3
	CYP4A22	ENST00000619754.4	TSL:1	c.454A>T	p.Asn152Tyr	missense	Exon 4 of 9	ENSP00000482952.1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85291 AN: 151800 Hom.: 27721 Cov.: 31

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

GnomAD2 exomes AF: 0.521 AC: 130675 AN: 250796 AF XY: 0.518

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 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.: 49 AF XY: 0.451 AC XY: 327570 AN XY: 726988

African (AFR) AF: 0.884 AC: 29574 AN: 33466

American (AMR) AF: 0.500 AC: 22324 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 8016 AN: 26100

East Asian (EAS) AF: 0.990 AC: 39304 AN: 39692

South Asian (SAS) AF: 0.673 AC: 57986 AN: 86152

European-Finnish (FIN) AF: 0.433 AC: 23139 AN: 53404

Middle Eastern (MID) AF: 0.429 AC: 2476 AN: 5766

European-Non Finnish (NFE) AF: 0.397 AC: 441248 AN: 1111738

Other (OTH) AF: 0.477 AC: 28817 AN: 60382

GnomAD4 genome AF: 0.562 AC: 85416 AN: 151920 Hom.: 27783 Cov.: 31 AF XY: 0.570 AC XY: 42318 AN XY: 74226

African (AFR) AF: 0.862 AC: 35739 AN: 41466

American (AMR) AF: 0.498 AC: 7608 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1094 AN: 3466

East Asian (EAS) AF: 0.979 AC: 5043 AN: 5152

South Asian (SAS) AF: 0.680 AC: 3266 AN: 4804

European-Finnish (FIN) AF: 0.432 AC: 4551 AN: 10542

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26507 AN: 67902

Other (OTH) AF: 0.505 AC: 1067 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.0
DANN	Benign	0.82
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.033	T
MetaRNN	Benign	0.0000015	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-3.5	N
PhyloP100		2.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	6.6	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.079
MPC		0.072
ClinPred		0.0050	T
GERP RS		0.25
Varity_R		0.044
gMVP		0.25
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2056899; hg19: chr1-47607851; COSMIC: COSV53739210;