1-47117831-G-C

Variant names:

• chr1-47117831-G-C
• NM_178134.3:c.1415G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_178134.3(CYP4Z1):​c.1415G>C​(p.Arg472Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R472H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYP4Z1 NM_178134.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345

Genes affected

CYP4Z1 (HGNC:20583): (cytochrome P450 family 4 subfamily Z member 1) 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. [provided by RefSeq, Jul 2008]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.818

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4Z1	NM_178134.3	c.1415G>C	p.Arg472Pro	missense_variant	Exon 12 of 12	ENST00000334194.4	NP_835235.1
CYP4Z1	XM_024453856.2	c.1301G>C	p.Arg434Pro	missense_variant	Exon 13 of 13		XP_024309624.1
CYP4A22-AS1	NR_189276.1	n.1115-19411C>G		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4Z1	ENST00000334194.4	c.1415G>C	p.Arg472Pro	missense_variant	Exon 12 of 12	1	NM_178134.3	ENSP00000334246.3
CYP4Z1	ENST00000471598.1	n.304G>C		non_coding_transcript_exon_variant	Exon 3 of 3	2
CYP4A22-AS1	ENST00000444042.2	n.397-20654C>G		intron_variant	Intron 3 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461442 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727028

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.072	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.010	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	3.7	H
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.57
MutPred		0.72		Loss of stability (P = 0.1028);
MVP		0.74
MPC		0.81
ClinPred		0.99	D
GERP RS		-1.4
Varity_R		0.93
gMVP		0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-47583503;