rs3919627

chr3-42867668-G-Achr3-42867668-G-T

Variant summary

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

The ENST00000437102.1(CYP8B1):c.1347+6802C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,642 control chromosomes in the GnomAD database, including 11,016 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 0.37 (11016 hom., cov: 30)
• Consequence: CYP8B1 ENST00000437102.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.888

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]

(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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP8B1	ENST00000437102.1	c.1347+6802C>T		intron_variant		1
	ENST00000471537.3	n.143-19870G>A		intron_variant, non_coding_transcript_variant		1
ACKR2	ENST00000460855.5	n.471+2809G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55341 AN: 151524 Hom.: 11005 Cov.: 30

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.365 AC: 55375 AN: 151642 Hom.: 11016 Cov.: 30 AF XY: 0.370 AC XY: 27437 AN XY: 74074

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.406

Alfa AF: 0.390 Hom.: 11840

Bravo AF: 0.383

Asia WGS AF: 0.497 AC: 1728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	5.8
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: rs3919627; hg19: chr3-42909160;