rs2056899

chr1-47142179-A-Gchr1-47142179-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001010969.4(CYP4A22):c.454A>G(p.Asn152Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N152Y) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CYP4A22 NM_001010969.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.18

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13687685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4A22	NM_001010969.4	c.454A>G	p.Asn152Asp	missense_variant	4/12	ENST00000371891.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4A22	ENST00000371891.8	c.454A>G	p.Asn152Asp	missense_variant	4/12	1	NM_001010969.4	P1
CYP4A22-AS1	ENST00000444042.2	n.396+34856T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	18
Dann	Uncertain	0.99
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.66	T;T;T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.79	N;.;N;N;.
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D;.;D;D;.
Sift4G	Uncertain	0.0050	D;D;D;D;D
Polyphen		0.039	B;.;.;B;.
Vest4		0.16
MutPred		0.67		Loss of ubiquitination at K156 (P = 0.1704);Loss of ubiquitination at K156 (P = 0.1704);Loss of ubiquitination at K156 (P = 0.1704);Loss of ubiquitination at K156 (P = 0.1704);Loss of ubiquitination at K156 (P = 0.1704);
MVP		0.11
MPC		0.068
ClinPred		0.60	D
GERP RS		0.25
Varity_R		0.36
gMVP		0.35

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

Other links and lift over

dbSNP: rs2056899; hg19: chr1-47607851;