chr1-46817100-C-T

Position:

• chr1-46817100-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Likely benign (no stars).

• 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

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034999251).
• BP6: Variant 1-46817100-C-T is Benign according to our data. Variant chr1-46817100-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4B1	NM_001099772.2	c.1126C>T	p.Arg376Cys	missense_variant	9/12	ENST00000371923.9	NP_001093242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4B1	ENST00000371923.9	c.1126C>T	p.Arg376Cys	missense_variant	9/12	1	NM_001099772.2	ENSP00000360991	A1

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

GnomAD3 exomes AF: 0.155 AC: 39057 AN: 251358 Hom.: 3221 AF XY: 0.152 AC XY: 20709 AN XY: 135852

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 SAS exome AF: 0.133

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

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.195

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.270

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.147

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

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.142

Alfa AF: 0.142 Hom.: 4137

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 v4.3

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;D;D
MetaRNN	Benign	0.0035	T;T;T
MetaSVM	Benign	-1.7	T
MutationAssessor	Pathogenic	4.5	.;H;.
MutationTaster	Benign	2.3e-10	P;P;P;P
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-7.6	D;D;D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.82
MPC		0.18
ClinPred		0.12	T
GERP RS		5.8
Varity_R		0.79
gMVP		0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs2297809; hg19: chr1-47282772; COSMIC: COSV54722621; COSMIC: COSV54722621;