NM_004820.5:c.1147G>T

Variant names:

• chr8-64604768-C-A
• NM_004820.5:c.1147G>T

Variant summary

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

The NM_004820.5(CYP7B1):​c.1147G>T​(p.Gly383Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CYP7B1 NM_004820.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703

Genes affected

CYP7B1 (HGNC:2652): (cytochrome P450 family 7 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 first reaction in the cholesterol catabolic pathway of extrahepatic tissues, which converts cholesterol to bile acids. This enzyme likely plays a minor role in total bile acid synthesis, but may also be involved in the development of atherosclerosis, neurosteroid metabolism and sex hormone synthesis. Mutations in this gene have been associated with hereditary spastic paraplegia (SPG5 or HSP), an autosomal recessive disorder. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP7B1	NM_004820.5	c.1147G>T	p.Gly383Trp	missense_variant	Exon 5 of 6	ENST00000310193.4	NP_004811.1
CYP7B1	NM_001324112.2	c.1147G>T	p.Gly383Trp	missense_variant	Exon 5 of 7		NP_001311041.1
CYP7B1	XM_017014002.2	c.1213G>T	p.Gly405Trp	missense_variant	Exon 6 of 7		XP_016869491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP7B1	ENST00000310193.4	c.1147G>T	p.Gly383Trp	missense_variant	Exon 5 of 6	1	NM_004820.5	ENSP00000310721.3
CYP7B1	ENST00000523954.1	n.421G>T		non_coding_transcript_exon_variant	Exon 3 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.81	D
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.038	D
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.66		Loss of disorder (P = 0.0279);
MVP		0.89
MPC		0.46
ClinPred		0.93	D
GERP RS		-1.0
Varity_R		0.22
gMVP		0.56

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: chr8-65517325;