rs1572603

Positions:

• chr1-46806731-G-A

Variant summary

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

The NM_001099772.2(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 NM_001099772.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.505

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4B1	NM_001099772.2	c.181-4077G>A		intron_variant		ENST00000371923.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4B1	ENST00000371923.9	c.181-4077G>A		intron_variant		1	NM_001099772.2	A1

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 15002 AN: 152138 Hom.: 890 Cov.: 32

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: 6 AN: 72 Hom.: 1 AF XY: 0.115 AC XY: 6 AN XY: 52

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.0577

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0986 AC: 15006 AN: 152256 Hom.: 890 Cov.: 32 AF XY: 0.101 AC XY: 7526 AN XY: 74448

Gnomad4 AFR AF: 0.0396

Gnomad4 AMR AF: 0.0987

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.0970

Alfa AF: 0.115 Hom.: 765

Bravo AF: 0.0929

Asia WGS AF: 0.184 AC: 639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.0
DANN	Benign	0.70

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: rs1572603; hg19: chr1-47272403;