NM_004820.5:c.*529A>G

Variant names:

• chr8-64596113-T-C
• rs113473170
• NM_004820.5:c.*529A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_004820.5(CYP7B1):​c.*529A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 162,290 control chromosomes in the GnomAD database, including 356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (355 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (1 hom.)
• Consequence: CYP7B1 NM_004820.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.14
• Publications: 2 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=-0.46).
• BP6: Variant 8-64596113-T-C is Benign according to our data. Variant chr8-64596113-T-C is described in ClinVar as Benign. ClinVar VariationId is 363574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 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.*529A>G		3_prime_UTR	Exon 6 of 6	NP_004811.1	O75881
	CYP7B1	NM_001324112.2		c.1234-6269A>G		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.*529A>G		3_prime_UTR	Exon 6 of 6	ENSP00000310721.3	O75881
	CYP7B1	ENST00000523954.1	TSL:3	n.508-6269A>G		intron	N/A
	CYP7B1	ENST00000864436.1		c.*529A>G		downstream_gene	N/A	ENSP00000534495.1

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5914 AN: 152168 Hom.: 355 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00156

Gnomad OTH AF: 0.0373

GnomAD4 exome AF: 0.00410 AC: 41 AN: 10004 Hom.: 1 Cov.: 0 AF XY: 0.00219 AC XY: 14 AN XY: 6388

African (AFR) AF: 0.151 AC: 23 AN: 152

American (AMR) AF: 0.0104 AC: 6 AN: 576

Ashkenazi Jewish (ASJ) AF: 0.00323 AC: 1 AN: 310

East Asian (EAS) AF: 0.00 AC: 0 AN: 240

South Asian (SAS) AF: 0.00110 AC: 4 AN: 3630

European-Finnish (FIN) AF: 0.000603 AC: 1 AN: 1658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 12

European-Non Finnish (NFE) AF: 0.00207 AC: 6 AN: 2896

Other (OTH) AF: 0.00 AC: 0 AN: 530

GnomAD4 genome AF: 0.0388 AC: 5916 AN: 152286 Hom.: 355 Cov.: 32 AF XY: 0.0376 AC XY: 2802 AN XY: 74466

African (AFR) AF: 0.130 AC: 5397 AN: 41540

American (AMR) AF: 0.0184 AC: 282 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4820

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00156 AC: 106 AN: 68018

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

Alfa AF: 0.0138 Hom.: 71

Bravo AF: 0.0442

Asia WGS AF: 0.0130 AC: 45 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary spastic paraplegia 5A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.69
PhyloP100		3.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs113473170; hg19: chr8-65508670;