rs8192871

Variant names:

• chr8-58499412-G-A
• rs8192871
• NM_000780.4:c.80+607C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-58499412-G-A
• chr8-58499412-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000780.4(CYP7A1):​c.80+607C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,028 control chromosomes in the GnomAD database, including 22,129 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 0.53 (22129 hom., cov: 33)
• Consequence: CYP7A1 NM_000780.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 7 publications found

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]

CYP7A1 Gene-Disease associations (from GenCC):

• hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency

  Inheritance: SD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP7A1	NM_000780.4	c.80+607C>T		intron_variant	Intron 1 of 5	ENST00000301645.4	NP_000771.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP7A1	ENST00000301645.4	c.80+607C>T		intron_variant	Intron 1 of 5	1	NM_000780.4	ENSP00000301645.3

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80752 AN: 151910 Hom.: 22108 Cov.: 33

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.532 AC: 80804 AN: 152028 Hom.: 22129 Cov.: 33 AF XY: 0.528 AC XY: 39255 AN XY: 74318

African (AFR) AF: 0.413 AC: 17147 AN: 41470

American (AMR) AF: 0.654 AC: 9991 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2228 AN: 3470

East Asian (EAS) AF: 0.430 AC: 2222 AN: 5170

South Asian (SAS) AF: 0.506 AC: 2439 AN: 4822

European-Finnish (FIN) AF: 0.486 AC: 5140 AN: 10586

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39717 AN: 67914

Other (OTH) AF: 0.560 AC: 1181 AN: 2108

Alfa AF: 0.566 Hom.: 30520

Bravo AF: 0.539

Asia WGS AF: 0.514 AC: 1787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.78
PhyloP100		0.20
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: rs8192871; hg19: chr8-59411971;