NM_001099772.2:c.203A>G

Variant names:

• chr1-46810830-A-G
• rs753724766
• NM_001099772.2:c.203A>G

Variant summary

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

The NM_001099772.2(CYP4B1):​c.203A>G​(p.Asp68Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000743 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: CYP4B1 NM_001099772.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.65
• 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.203A>G	p.Asp68Gly	missense	Exon 2 of 12	NP_001093242.1	P13584-2
	CYP4B1	NM_000779.4		c.203A>G	p.Asp68Gly	missense	Exon 2 of 12	NP_000770.2	P13584-1
	CYP4B1	NM_001319161.2		c.203A>G	p.Asp68Gly	missense	Exon 2 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.203A>G	p.Asp68Gly	missense	Exon 2 of 12	ENSP00000360991.4	P13584-2
	CYP4B1	ENST00000271153.8	TSL:1	c.203A>G	p.Asp68Gly	missense	Exon 2 of 12	ENSP00000271153.4	P13584-1
	CYP4B1	ENST00000371919.8	TSL:1	c.203A>G	p.Asp68Gly	missense	Exon 2 of 11	ENSP00000360987.4	Q8IZB0

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251334 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727242

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: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00000719 AC: 8 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74316

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.033
Eigen_PC	Benign	0.068
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.024	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.6
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.22
Sift	Benign	0.072	T
Sift4G	Benign	0.29	T
Polyphen		0.0080	B
Vest4		0.64
MutPred		0.37		Loss of stability (P = 0.0238)
MVP		0.80
MPC		0.40
ClinPred		0.75	D
GERP RS		5.3
Varity_R		0.43
gMVP		0.52
Mutation Taster		=88/12	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: rs753724766; hg19: chr1-47276502;