rs837398

Positions:

• chr1-46800750-T-A
• chr1-46800750-T-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4B1	NM_001099772.2	c.180+1489T>A		intron_variant		ENST00000371923.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4B1	ENST00000371923.9	c.180+1489T>A		intron_variant		1	NM_001099772.2	A1

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

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.791

Gnomad4 ASJ AF: 0.836

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.790

Gnomad4 NFE AF: 0.806

Gnomad4 OTH AF: 0.741

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.82

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

LitVar

Other links and lift over

dbSNP: rs837398; hg19: chr1-47266422;