dbSNP rs12059860: CYP4B1:c.*437T>C (chr1-46819251-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001099772.2(CYP4B1):c.*437T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 159,584 control chromosomes in the GnomAD database, including 246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.039 ( 242 hom., cov: 32)

Exomes 𝑓: 0.017 ( 4 hom. )

Consequence

CYP4B1
NM_001099772.2 3_prime_UTR

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 0.622

Publications

7 publications found

Variant links:

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]

CYP4B1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4B1	NM_001099772.2 link	c.*437T>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000371923.9	NP_001093242.1	P13584-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4B1	ENST00000371923.9 link	c.*437T>C		3_prime_UTR_variant	Exon 12 of 12	1	NM_001099772.2	ENSP00000360991.4		P13584-2

Frequencies

GnomAD3 genomes

AF:

0.0385

AC:

5864

AN:

152196

Hom.:

239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0691

Gnomad FIN

AF:

0.00734

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0120

Gnomad OTH

AF:

0.0325

GnomAD4 exome

AF:

0.0166

AC:

121

AN:

7270

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

AN XY:

3722

show subpopulations

African (AFR)

AF:

0.118

AC:

AN:

152

American (AMR)

AF:

0.0112

AC:

AN:

800

Ashkenazi Jewish (ASJ)

AF:

0.0118

AC:

AN:

170

East Asian (EAS)

AF:

0.00

AC:

AN:

282

South Asian (SAS)

AF:

0.0799

AC:

AN:

288

European-Finnish (FIN)

AF:

0.00980

AC:

AN:

204

Middle Eastern (MID)

AF:

0.100

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0115

AC:

AN:

4974

Other (OTH)

AF:

0.0189

AC:

AN:

370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0386

AC:

5883

AN:

152314

Hom.:

242

Cov.:

AF XY:

0.0382

AC XY:

2849

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0991

AC:

4120

AN:

41554

American (AMR)

AF:

0.0244

AC:

374

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0228

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.0694

AC:

335

AN:

4828

European-Finnish (FIN)

AF:

0.00734

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0120

AC:

818

AN:

68032

Other (OTH)

AF:

0.0321

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

264

527

791

1054

1318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0201

Hom.:

288

Bravo

AF:

0.0410

Asia WGS

AF:

0.0320

AC:

111

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Pulmonary disease, chronic obstructive, susceptibility to

Other:1

Jul 05, 2022

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance:association

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

9.3

(source)

DANN

Benign

0.72

PhyloP100

0.62

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over