chr3-42872520-T-C

Position:

• chr3-42872520-T-C

Variant summary

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

The NM_004391.3(CYP8B1):​c.*1791A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 152,084 control chromosomes in the GnomAD database, including 27,271 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 0.59 (27263 hom., cov: 32)
  • Exomes 𝑓: 0.57 (8 hom.)
• Consequence: CYP8B1 NM_004391.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

Genes affected

CYP8B1 (HGNC:2653): (cytochrome P450 family 8 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 endoplasmic reticulum membrane protein catalyzes the conversion of 7 alpha-hydroxy-4-cholesten-3-one into 7-alpha,12-alpha-dihydroxy-4-cholesten-3-one. The balance between these two steroids determines the relative amounts of cholic acid and chenodeoxycholic acid both of which are secreted in the bile and affect the solubility of cholesterol. This gene is unique among the cytochrome P450 genes in that it is intronless. [provided by RefSeq, Jul 2008]

ENSG00000290317 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP8B1	NM_004391.3	c.*1791A>G		3_prime_UTR_variant	1/1	ENST00000316161.6	NP_004382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP8B1	ENST00000316161.6	c.*1791A>G		3_prime_UTR_variant	1/1	6	NM_004391.3	ENSP00000318867.4
ENSG00000290317	ENST00000426937.5	c.-163-36273T>C		intron_variant		3		ENSP00000413859.1

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89776 AN: 151922 Hom.: 27229 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.574

GnomAD4 exome AF: 0.568 AC: 25 AN: 44 Hom.: 8 Cov.: 0 AF XY: 0.615 AC XY: 16 AN XY: 26

Gnomad4 AFR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.533

GnomAD4 genome AF: 0.591 AC: 89873 AN: 152040 Hom.: 27263 Cov.: 32 AF XY: 0.595 AC XY: 44196 AN XY: 74320

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.815

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.578

Alfa AF: 0.528 Hom.: 44435

Bravo AF: 0.612

Asia WGS AF: 0.709 AC: 2467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.29
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs3732860; hg19: chr3-42914012;