NM_001099772.2:c.180+1489T>A

Variant names:

• chr1-46800750-T-A
• rs837398
• NM_001099772.2:c.180+1489T>A

Variant summary

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

The NM_001099772.2(CYP4B1):​c.180+1489T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,012 control chromosomes in the GnomAD database, including 40,406 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 0.72 (40406 hom., cov: 30)
• Consequence: CYP4B1 NM_001099772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 2 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=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.801 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.180+1489T>A		intron	N/A	NP_001093242.1
	CYP4B1	NM_000779.4		c.180+1489T>A		intron	N/A	NP_000770.2
	CYP4B1	NM_001319161.2		c.180+1489T>A		intron	N/A	NP_001306090.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4B1	ENST00000371923.9	TSL:1 MANE Select	c.180+1489T>A		intron	N/A	ENSP00000360991.4
	CYP4B1	ENST00000271153.8	TSL:1	c.180+1489T>A		intron	N/A	ENSP00000271153.4
	CYP4B1	ENST00000371919.8	TSL:1	c.180+1489T>A		intron	N/A	ENSP00000360987.4

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109152 AN: 151894 Hom.: 40398 Cov.: 30

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.791

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.738

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.718 AC: 109199 AN: 152012 Hom.: 40406 Cov.: 30 AF XY: 0.718 AC XY: 53346 AN XY: 74270

African (AFR) AF: 0.525 AC: 21749 AN: 41414

American (AMR) AF: 0.791 AC: 12094 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2902 AN: 3470

East Asian (EAS) AF: 0.714 AC: 3677 AN: 5148

South Asian (SAS) AF: 0.632 AC: 3042 AN: 4814

European-Finnish (FIN) AF: 0.790 AC: 8359 AN: 10580

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54820 AN: 67988

Other (OTH) AF: 0.741 AC: 1560 AN: 2106

Alfa AF: 0.789 Hom.: 26373

Bravo AF: 0.711

Asia WGS AF: 0.663 AC: 2303 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.82
PhyloP100		1.3
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: rs837398; hg19: chr1-47266422;