rs10808738

Variant names:

• chr8-64631568-G-A
• rs10808738
• NM_004820.5:c.123-7029C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

CYP7B1 Gene-Disease associations (from GenCC):

• CYP7B1-related disorder of oxysterol accumulation

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• congenital bile acid synthesis defect 3

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary spastic paraplegia 5A

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004820.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP7B1	NM_004820.5	MANE Select	c.123-7029C>T		intron	N/A	NP_004811.1	O75881
	CYP7B1	NM_001324112.2		c.123-7029C>T		intron	N/A	NP_001311041.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP7B1	ENST00000310193.4	TSL:1 MANE Select	c.123-7029C>T		intron	N/A	ENSP00000310721.3	O75881
	CYP7B1	ENST00000864436.1		c.276-7029C>T		intron	N/A	ENSP00000534495.1
	CYP7B1	ENST00000864435.1		c.123-7029C>T		intron	N/A	ENSP00000534494.1

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

African (AFR) AF: 0.305 AC: 12617 AN: 41424

American (AMR) AF: 0.523 AC: 7990 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2018 AN: 3470

East Asian (EAS) AF: 0.437 AC: 2260 AN: 5170

South Asian (SAS) AF: 0.407 AC: 1965 AN: 4826

European-Finnish (FIN) AF: 0.718 AC: 7571 AN: 10544

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39393 AN: 67932

Other (OTH) AF: 0.506 AC: 1066 AN: 2108

Alfa AF: 0.559 Hom.: 38317

Bravo AF: 0.479

Asia WGS AF: 0.395 AC: 1373 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.84
DANN	Benign	0.61
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10808738; hg19: chr8-65544125;