rs1572603

Variant names:

• chr1-46806731-G-A
• rs1572603
• NM_001099772.2:c.181-4077G>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.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
• 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=-0.77).
• 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 rank	MANE	Protein	UniProt
CYP4B1	NM_001099772.2	c.181-4077G>A		intron_variant	Intron 1 of 11	ENST00000371923.9	NP_001093242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4B1	ENST00000371923.9	c.181-4077G>A		intron_variant	Intron 1 of 11	1	NM_001099772.2	ENSP00000360991.4

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0577 AC: 3 AN: 52

Other (OTH) AF: 0.100 AC: 1 AN: 10

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

African (AFR) AF: 0.0396 AC: 1643 AN: 41532

American (AMR) AF: 0.0987 AC: 1511 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 348 AN: 3472

East Asian (EAS) AF: 0.192 AC: 998 AN: 5188

South Asian (SAS) AF: 0.186 AC: 898 AN: 4824

European-Finnish (FIN) AF: 0.122 AC: 1290 AN: 10596

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7969 AN: 68018

Other (OTH) AF: 0.0970 AC: 205 AN: 2114

Alfa AF: 0.113 Hom.: 892

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
PhyloP100		0.51
PromoterAI		-0.082	Neutral
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: rs1572603; hg19: chr1-47272403;