rs11786580

Variant names:

• chr8-58493381-C-T
• rs11786580
• NM_000780.4:c.1040-853G>A

Variant summary

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

The NM_000780.4(CYP7A1):​c.1040-853G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,064 control chromosomes in the GnomAD database, including 2,738 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 0.19 (2738 hom., cov: 32)
• Consequence: CYP7A1 NM_000780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP7A1	NM_000780.4	c.1040-853G>A		intron_variant	Intron 4 of 5	ENST00000301645.4	NP_000771.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP7A1	ENST00000301645.4	c.1040-853G>A		intron_variant	Intron 4 of 5	1	NM_000780.4	ENSP00000301645.3

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28250 AN: 151946 Hom.: 2739 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.0781

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.186 AC: 28259 AN: 152064 Hom.: 2738 Cov.: 32 AF XY: 0.180 AC XY: 13403 AN XY: 74362

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.0786

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.204

Alfa AF: 0.202 Hom.: 4399

Bravo AF: 0.189

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.016
DANN	Benign	0.63

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: rs11786580; hg19: chr8-59405940;