rs10808739

Positions:

• chr8-64727703-G-A

Variant summary

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

The NM_004820.5(CYP7B1):​c.122+70763C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 151,952 control chromosomes in the GnomAD database, including 4,641 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 0.23 (4641 hom., cov: 32)
• Consequence: CYP7B1 NM_004820.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP7B1	NM_004820.5	c.122+70763C>T		intron_variant		ENST00000310193.4	NP_004811.1
CYP7B1	NM_001324112.2	c.122+70763C>T		intron_variant			NP_001311041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP7B1	ENST00000310193.4	c.122+70763C>T		intron_variant		1	NM_004820.5	ENSP00000310721	P1
	ENST00000519680.1	n.509+251C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35450 AN: 151832 Hom.: 4644 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0288

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.233 AC: 35455 AN: 151952 Hom.: 4641 Cov.: 32 AF XY: 0.229 AC XY: 16978 AN XY: 74272

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0289

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.225

Alfa AF: 0.211 Hom.: 6517

Bravo AF: 0.238

Asia WGS AF: 0.102 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.77

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: rs10808739; hg19: chr8-65640260;