rs1424428588

Variant names:

• chr1-46813545-A-G
• rs1424428588
• NM_001099772.2:c.559A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-46813545-A-G
• chr1-46813545-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001099772.2(CYP4B1):​c.559A>G​(p.Met187Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M187L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYP4B1 NM_001099772.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.81
• Publications: 0 publications found

Genes affected

CYP4B1 (HGNC:2644): (cytochrome P450 family 4 subfamily B 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 protein localizes to the endoplasmic reticulum. In rodents, the homologous protein has been shown to metabolize certain carcinogens; however, the specific function of the human protein has not been determined. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099772.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4B1	NM_001099772.2	MANE Select	c.559A>G	p.Met187Val	missense	Exon 5 of 12	NP_001093242.1	P13584-2
	CYP4B1	NM_000779.4		c.559A>G	p.Met187Val	missense	Exon 5 of 12	NP_000770.2	P13584-1
	CYP4B1	NM_001319161.2		c.514A>G	p.Met172Val	missense	Exon 4 of 11	NP_001306090.1	Q8IZB0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4B1	ENST00000371923.9	TSL:1 MANE Select	c.559A>G	p.Met187Val	missense	Exon 5 of 12	ENSP00000360991.4	P13584-2
	CYP4B1	ENST00000271153.8	TSL:1	c.559A>G	p.Met187Val	missense	Exon 5 of 12	ENSP00000271153.4	P13584-1
	CYP4B1	ENST00000371919.8	TSL:1	c.514A>G	p.Met172Val	missense	Exon 4 of 11	ENSP00000360987.4	Q8IZB0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000370 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	18
DANN	Benign	0.89
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.16
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		6.8
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.034	D
Polyphen		0.049	B
Vest4		0.50
MVP		0.54
MPC		0.091
ClinPred		0.93	D
GERP RS		3.9
Varity_R		0.90
gMVP		0.63
Mutation Taster		=87/13	polymorphism

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: rs1424428588; hg19: chr1-47279217;