rs8192871

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.68).
• 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/exons	MANE	UniProt
CYP7A1	NM_000780.4	c.80+607C>T		intron_variant		ENST00000301645.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP7A1	ENST00000301645.4	c.80+607C>T		intron_variant		1	NM_000780.4	P1

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

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.486

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.560

Alfa AF: 0.567 Hom.: 22936

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

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: rs8192871; hg19: chr8-59411971;