1-47137534-G-C

Variant names:

• chr1-47137534-G-C
• rs369829008
• NM_001010969.4:c.49G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001010969.4(CYP4A22):​c.49G>C​(p.Gly17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CYP4A22 NM_001010969.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3056371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4A22	NM_001010969.4	c.49G>C	p.Gly17Arg	missense_variant	Exon 1 of 12	ENST00000371891.8	NP_001010969.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4A22	ENST00000371891.8	c.49G>C	p.Gly17Arg	missense_variant	Exon 1 of 12	1	NM_001010969.4	ENSP00000360958.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461828 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	.;.;.;T;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.78	T;T;T;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.31	T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.0	.;.;.;M;.
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.7	D;.;N;N;.
REVEL	Uncertain	0.43
Sift	Benign	0.27	T;.;T;T;.
Sift4G	Benign	0.21	T;T;T;T;T
Polyphen		0.99	D;.;.;P;.
Vest4		0.59
MutPred		0.65		Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);Gain of MoRF binding (P = 0.0166);
MVP		0.43
MPC		0.13
ClinPred		0.45	T
GERP RS		1.6
Varity_R		0.059
gMVP		0.24

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: rs369829008; hg19: chr1-47603206;