3-42872520-T-C

Variant names:

• chr3-42872520-T-C
• rs3732860
• NM_004391.3:c.*1791A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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:):

ACKR2 (HGNC:1565): (atypical chemokine receptor 2) This gene encodes a beta chemokine receptor, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. Chemokines and their receptor-mediated signal transduction are critical for the recruitment of effector immune cells to the inflammation site. This gene is expressed in a range of tissues and hemopoietic cells. The expression of this receptor in lymphatic endothelial cells and overexpression in vascular tumors suggested its function in chemokine-driven recirculation of leukocytes and possible chemokine effects on the development and growth of vascular tumors. This receptor appears to bind the majority of beta-chemokine family members; however, its specific function remains unknown. This gene is mapped to chromosome 3p21.3, a region that includes a cluster of chemokine receptor genes. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYP8B1	NM_004391.3	c.*1791A>G		3_prime_UTR_variant	Exon 1 of 1	ENST00000316161.6	NP_004382.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP8B1	ENST00000316161.6	c.*1791A>G		3_prime_UTR_variant	Exon 1 of 1	6	NM_004391.3	ENSP00000318867.4
ENSG00000290317	ENST00000426937.5	c.-163-36273T>C		intron_variant	Intron 2 of 6	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

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.533 AC: 16 AN: 30

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.690 AC: 28606 AN: 41448

American (AMR) AF: 0.680 AC: 10394 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1577 AN: 3466

East Asian (EAS) AF: 0.815 AC: 4198 AN: 5154

South Asian (SAS) AF: 0.628 AC: 3023 AN: 4814

European-Finnish (FIN) AF: 0.527 AC: 5577 AN: 10574

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34640 AN: 67984

Other (OTH) AF: 0.578 AC: 1220 AN: 2110

Alfa AF: 0.536 Hom.: 94626

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
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3732860; hg19: chr3-42914012;