1-47137517-G-T

Variant names:

• chr1-47137517-G-T
• rs200538871
• NM_001010969.4:c.32G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001010969.4(CYP4A22):​c.32G>T​(p.Arg11Leu) 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 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. R11H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYP4A22 NM_001010969.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023907423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4A22	NM_001010969.4	c.32G>T	p.Arg11Leu	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.32G>T	p.Arg11Leu	missense_variant	Exon 1 of 12	1	NM_001010969.4	ENSP00000360958.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250878 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135580

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461652 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727122

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.24
DANN	Benign	0.73
DEOGEN2	Benign	0.0083	.;.;.;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00052	N
LIST_S2	Benign	0.0084	T;T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.024	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-1.9	.;.;.;N;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	2.0	N;.;N;N;.
REVEL	Benign	0.048
Sift	Benign	0.72	T;.;T;T;.
Sift4G	Benign	0.68	T;T;T;T;T
Polyphen		0.0	B;.;.;B;.
Vest4		0.11
MutPred		0.39		Loss of methylation at R11 (P = 0.0095);Loss of methylation at R11 (P = 0.0095);Loss of methylation at R11 (P = 0.0095);Loss of methylation at R11 (P = 0.0095);Loss of methylation at R11 (P = 0.0095);
MVP		0.048
MPC		0.073
ClinPred		0.036	T
GERP RS		-3.0
Varity_R		0.037
gMVP		0.28

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: rs200538871; hg19: chr1-47603189;