1-46803666-T-A

Position:

• chr1-46803666-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099772.2(CYP4B1):​c.180+4405T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,092 control chromosomes in the GnomAD database, including 45,679 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 0.77 (45679 hom., cov: 31)
• Consequence: CYP4B1 NM_001099772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4B1	NM_001099772.2	c.180+4405T>A		intron_variant		ENST00000371923.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4B1	ENST00000371923.9	c.180+4405T>A		intron_variant		1	NM_001099772.2	A1

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117449 AN: 151974 Hom.: 45648 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.789

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

GnomAD4 genome AF: 0.773 AC: 117530 AN: 152092 Hom.: 45679 Cov.: 31 AF XY: 0.772 AC XY: 57374 AN XY: 74348

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.806

Gnomad4 EAS AF: 0.791

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.791

Alfa AF: 0.797 Hom.: 6038

Bravo AF: 0.774

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.51

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: rs837395; hg19: chr1-47269338; COSMIC: COSV54726277; COSMIC: COSV54726277;