dbSNP rs1572603: CYP4B1:c.181-4077G>A (chr1-46806731-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000371923.9(CYP4B1):c.181-4077G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 152,328 control chromosomes in the GnomAD database, including 891 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 0.099 ( 890 hom., cov: 32)

Exomes 𝑓: 0.083 ( 1 hom. )

Consequence

CYP4B1
ENST00000371923.9 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.505

Publications

2 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=-0.77).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371923.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYP4B1	NM_001099772.2	MANE Select	c.181-4077G>A	intron	N/A	NP_001093242.1
CYP4B1	NM_000779.4		c.181-4077G>A	intron	N/A	NP_000770.2
CYP4B1	NM_001319161.2		c.181-4077G>A	intron	N/A	NP_001306090.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYP4B1	ENST00000371923.9	TSL:1 MANE Select	c.181-4077G>A	intron	N/A	ENSP00000360991.4
CYP4B1	ENST00000271153.8	TSL:1	c.181-4077G>A	intron	N/A	ENSP00000271153.4
CYP4B1	ENST00000371919.8	TSL:1	c.181-4077G>A	intron	N/A	ENSP00000360987.4

Frequencies

GnomAD3 genomes

AF:

0.0986

AC:

15002

AN:

152138

Hom.:

890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0396

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0986

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.0975

GnomAD4 exome

AF:

0.0833

AC:

AN:

Hom.:

AF XY:

0.115

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0577

AC:

AN:

Other (OTH)

AF:

0.100

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0986

AC:

15006

AN:

152256

Hom.:

890

Cov.:

AF XY:

0.101

AC XY:

7526

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0396

AC:

1643

AN:

41532

American (AMR)

AF:

0.0987

AC:

1511

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

348

AN:

3472

East Asian (EAS)

AF:

0.192

AC:

998

AN:

5188

South Asian (SAS)

AF:

0.186

AC:

898

AN:

4824

European-Finnish (FIN)

AF:

0.122

AC:

1290

AN:

10596

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7969

AN:

68018

Other (OTH)

AF:

0.0970

AC:

205

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

690

1381

2071

2762

3452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<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:

0.113

Hom.:

892

Bravo

AF:

0.0929

Asia WGS

AF:

0.184

AC:

639

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.0

(source)

DANN

Benign

0.70

PhyloP100

0.51

PromoterAI

-0.082

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over