3-42874733-C-T

Position:

• chr3-42874733-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004391.3(CYP8B1):​c.1084G>A​(p.Glu362Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYP8B1 NM_004391.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.36

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07142612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP8B1	NM_004391.3	c.1084G>A	p.Glu362Lys	missense_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.1084G>A	p.Glu362Lys	missense_variant	1/1	6	NM_004391.3	ENSP00000318867.4
ENSG00000290317	ENST00000426937.5	c.-163-34060C>T		intron_variant		3		ENSP00000413859.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2024

The c.1084G>A (p.E362K) alteration is located in exon 1 (coding exon 1) of the CYP8B1 gene. This alteration results from a G to A substitution at nucleotide position 1084, causing the glutamic acid (E) at amino acid position 362 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.046
DANN	Benign	0.83
DEOGEN2	Benign	0.030	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.96	.;L
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.027
Sift	Benign	0.32	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.0090	B;B
Vest4		0.13
MutPred		0.59		Gain of MoRF binding (P = 0.0259);Gain of MoRF binding (P = 0.0259);
MVP		0.014
MPC		0.13
ClinPred		0.11	T
GERP RS		-1.9
Varity_R		0.046
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-42916225;