rs8192877

chr8-58491882-A-Gchr8-58491882-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000780.4(CYP7A1):c.1216-108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 904,936 control chromosomes in the GnomAD database, including 8,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1237 hom., cov: 32)
  • Exomes 𝑓: 0.13 (6993 hom.)
• Consequence: CYP7A1 NM_000780.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.26

Genes affected

CYP7A1 (HGNC:2651): (cytochrome P450 family 7 subfamily A 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 in the liver, which converts cholesterol to bile acids. This reaction is the rate limiting step and the major site of regulation of bile acid synthesis, which is the primary mechanism for the removal of cholesterol from the body. Polymorphisms in the promoter of this gene are associated with defects in bile acid synthesis. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 8-58491882-A-G is Benign according to our data. Variant chr8-58491882-A-G is described in ClinVar as [Benign]. Clinvar id is 1235467.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP7A1	NM_000780.4	c.1216-108T>C		intron_variant		ENST00000301645.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP7A1	ENST00000301645.4	c.1216-108T>C		intron_variant		1	NM_000780.4	P1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18866 AN: 152150 Hom.: 1238 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.0377

Gnomad SAS AF: 0.0841

Gnomad FIN AF: 0.0774

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.130 AC: 97707 AN: 752670 Hom.: 6993 AF XY: 0.129 AC XY: 51296 AN XY: 397202

Gnomad4 AFR exome AF: 0.102

Gnomad4 AMR exome AF: 0.0780

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.0473

Gnomad4 SAS exome AF: 0.0859

Gnomad4 FIN exome AF: 0.0967

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.124 AC: 18862 AN: 152266 Hom.: 1237 Cov.: 32 AF XY: 0.120 AC XY: 8970 AN XY: 74456

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.0380

Gnomad4 SAS AF: 0.0842

Gnomad4 FIN AF: 0.0774

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.139

Alfa AF: 0.142 Hom.: 2114

Bravo AF: 0.126

Asia WGS AF: 0.0590 AC: 205 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.5
Dann	Benign	0.80

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: rs8192877; hg19: chr8-59404441;