1-46817100-C-T

Variant names:

• chr1-46817100-C-T
• rs2297809
• NM_001099772.2:c.1126C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099772.2(CYP4B1):​c.1126C>T​(p.Arg376Cys) variant causes a missense change. The variant allele was found at a frequency of 0.143 in 1,613,874 control chromosomes in the GnomAD database, including 17,222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1742 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15480 hom.)
• Consequence: CYP4B1 NM_001099772.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01
• Publications: 44 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034999251).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4B1	NM_001099772.2	MANE Select	c.1126C>T	p.Arg376Cys	missense	Exon 9 of 12	NP_001093242.1
	CYP4B1	NM_000779.4		c.1123C>T	p.Arg375Cys	missense	Exon 9 of 12	NP_000770.2
	CYP4B1	NM_001319161.2		c.1081C>T	p.Arg361Cys	missense	Exon 8 of 11	NP_001306090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4B1	ENST00000371923.9	TSL:1 MANE Select	c.1126C>T	p.Arg376Cys	missense	Exon 9 of 12	ENSP00000360991.4
	CYP4B1	ENST00000271153.8	TSL:1	c.1123C>T	p.Arg375Cys	missense	Exon 9 of 12	ENSP00000271153.4
	CYP4B1	ENST00000371919.8	TSL:1	c.1081C>T	p.Arg361Cys	missense	Exon 8 of 11	ENSP00000360987.4

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22324 AN: 152046 Hom.: 1734 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.145

GnomAD2 exomes AF: 0.155 AC: 39057 AN: 251358 AF XY: 0.152

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.125

Gnomad EAS exome AF: 0.242

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.143

Gnomad OTH exome AF: 0.146

GnomAD4 exome AF: 0.142 AC: 208237 AN: 1461710 Hom.: 15480 Cov.: 32 AF XY: 0.142 AC XY: 103466 AN XY: 727162

African (AFR) AF: 0.131 AC: 4372 AN: 33478

American (AMR) AF: 0.195 AC: 8718 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 3379 AN: 26130

East Asian (EAS) AF: 0.270 AC: 10717 AN: 39694

South Asian (SAS) AF: 0.139 AC: 11983 AN: 86250

European-Finnish (FIN) AF: 0.146 AC: 7784 AN: 53416

Middle Eastern (MID) AF: 0.110 AC: 633 AN: 5768

European-Non Finnish (NFE) AF: 0.136 AC: 151759 AN: 1111868

Other (OTH) AF: 0.147 AC: 8892 AN: 60392

GnomAD4 genome AF: 0.147 AC: 22341 AN: 152164 Hom.: 1742 Cov.: 32 AF XY: 0.149 AC XY: 11114 AN XY: 74372

African (AFR) AF: 0.135 AC: 5602 AN: 41502

American (AMR) AF: 0.192 AC: 2930 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3472

East Asian (EAS) AF: 0.254 AC: 1310 AN: 5158

South Asian (SAS) AF: 0.135 AC: 651 AN: 4830

European-Finnish (FIN) AF: 0.144 AC: 1522 AN: 10590

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9418 AN: 68008

Other (OTH) AF: 0.142 AC: 299 AN: 2112

Alfa AF: 0.144 Hom.: 8011

Bravo AF: 0.148

TwinsUK AF: 0.135 AC: 500

ALSPAC AF: 0.128 AC: 493

ESP6500AA AF: 0.133 AC: 587

ESP6500EA AF: 0.143 AC: 1228

ExAC AF: 0.155 AC: 18875

Asia WGS AF: 0.198 AC: 690 AN: 3478

EpiCase AF: 0.140

EpiControl AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Pathogenic	0.27
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-1.7	T
MutationAssessor	Pathogenic	4.5	H
PhyloP100		5.0
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-7.6	D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.82
MPC		0.18
ClinPred		0.12	T
GERP RS		5.8
Varity_R		0.79
gMVP		0.89
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2297809; hg19: chr1-47282772; COSMIC: COSV54722621; COSMIC: COSV54722621;