rs12059860

Variant names:

• chr1-46819251-T-C
• rs12059860
• NM_001099772.2:c.*437T>C

Variant summary

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

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
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.622
• Publications: 7 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 (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4B1	NM_001099772.2	MANE Select	c.*437T>C		3_prime_UTR	Exon 12 of 12	NP_001093242.1	P13584-2
	CYP4B1	NM_000779.4		c.*437T>C		3_prime_UTR	Exon 12 of 12	NP_000770.2	P13584-1
	CYP4B1	NM_001319161.2		c.*437T>C		3_prime_UTR	Exon 11 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.*437T>C		3_prime_UTR	Exon 12 of 12	ENSP00000360991.4	P13584-2
	CYP4B1	ENST00000271153.8	TSL:1	c.*437T>C		3_prime_UTR	Exon 12 of 12	ENSP00000271153.4	P13584-1
	CYP4B1	ENST00000887999.1		c.*437T>C		3_prime_UTR	Exon 12 of 12	ENSP00000558058.1

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5864 AN: 152196 Hom.: 239 Cov.: 32

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.: 4 Cov.: 0 AF XY: 0.0180 AC XY: 67 AN XY: 3722

African (AFR) AF: 0.118 AC: 18 AN: 152

American (AMR) AF: 0.0112 AC: 9 AN: 800

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 2 AN: 170

East Asian (EAS) AF: 0.00 AC: 0 AN: 282

South Asian (SAS) AF: 0.0799 AC: 23 AN: 288

European-Finnish (FIN) AF: 0.00980 AC: 2 AN: 204

Middle Eastern (MID) AF: 0.100 AC: 3 AN: 30

European-Non Finnish (NFE) AF: 0.0115 AC: 57 AN: 4974

Other (OTH) AF: 0.0189 AC: 7 AN: 370

GnomAD4 genome AF: 0.0386 AC: 5883 AN: 152314 Hom.: 242 Cov.: 32 AF XY: 0.0382 AC XY: 2849 AN XY: 74490

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: 79 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.0694 AC: 335 AN: 4828

European-Finnish (FIN) AF: 0.00734 AC: 78 AN: 10626

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 818 AN: 68032

Other (OTH) AF: 0.0321 AC: 68 AN: 2116

Alfa AF: 0.0201 Hom.: 288

Bravo AF: 0.0410

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Pulmonary disease, chronic obstructive, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.3
DANN	Benign	0.72
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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: rs12059860; hg19: chr1-47284923; COSMIC: COSV54722193; COSMIC: COSV54722193;