rs10808738

chr8-64631568-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.123-7029C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,946 control chromosomes in the GnomAD database, including 20,232 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 0.50 (20232 hom., cov: 32)
• Consequence: CYP7B1 NM_004820.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP7B1	NM_004820.5	c.123-7029C>T		intron_variant		ENST00000310193.4
CYP7B1	NM_001324112.2	c.123-7029C>T		intron_variant
CYP7B1	XM_017014002.2	c.189-7029C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP7B1	ENST00000310193.4	c.123-7029C>T		intron_variant		1	NM_004820.5	P1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75706 AN: 151828 Hom.: 20233 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.498 AC: 75726 AN: 151946 Hom.: 20232 Cov.: 32 AF XY: 0.503 AC XY: 37348 AN XY: 74274

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.506

Alfa AF: 0.562 Hom.: 32365

Bravo AF: 0.479

Asia WGS AF: 0.395 AC: 1373 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.84
Dann	Benign	0.61

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: rs10808738; hg19: chr8-65544125;