Genetic Variant CYP7A1:c.-267C>A (chr8-58500365-G-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000780.4(CYP7A1):c.-267C>A variant causes a upstream gene change. The variant allele was found at a frequency of 0.568 in 407,118 control chromosomes in the GnomAD database, including 66,983 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23418 hom., cov: 32)

Exomes 𝑓: 0.58 ( 43565 hom. )

Consequence

CYP7A1
NM_000780.4 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.25

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 8-58500365-G-T is Benign according to our data. Variant chr8-58500365-G-T is described in ClinVar as [Benign]. Clinvar id is 1229509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP7A1	NM_000780.4 link	c.-267C>A		upstream_gene_variant		ENST00000301645.4	NP_000771.2	P22680

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP7A1	ENST00000301645.4 link	c.-267C>A		upstream_gene_variant		1	NM_000780.4	ENSP00000301645.3		P22680

Frequencies

GnomAD3 genomes

AF:

0.548

AC:

83111

AN:

151748

Hom.:

23399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.604

Gnomad AMR

AF:

0.663

Gnomad ASJ

AF:

0.654

Gnomad EAS

AF:

0.537

Gnomad SAS

AF:

0.569

Gnomad FIN

AF:

0.488

Gnomad MID

AF:

0.666

Gnomad NFE

AF:

0.601

Gnomad OTH

AF:

0.567

GnomAD4 exome

AF:

0.581

AC:

148203

AN:

255252

Hom.:

43565

AF XY:

0.578

AC XY:

78587

AN XY:

135926

show subpopulations

Gnomad4 AFR exome

AF:

0.411

Gnomad4 AMR exome

AF:

0.683

Gnomad4 ASJ exome

AF:

0.644

Gnomad4 EAS exome

AF:

0.519

Gnomad4 SAS exome

AF:

0.551

Gnomad4 FIN exome

AF:

0.519

Gnomad4 NFE exome

AF:

0.596

Gnomad4 OTH exome

AF:

0.589

GnomAD4 genome

AF:

0.548

AC:

83159

AN:

151866

Hom.:

23418

Cov.:

AF XY:

0.545

AC XY:

40441

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.419

Gnomad4 AMR

AF:

0.663

Gnomad4 ASJ

AF:

0.654

Gnomad4 EAS

AF:

0.538

Gnomad4 SAS

AF:

0.567

Gnomad4 FIN

AF:

0.488

Gnomad4 NFE

AF:

0.601

Gnomad4 OTH

AF:

0.573

Alfa

AF:

0.593

Hom.:

41179

Bravo

AF:

0.555

Asia WGS

AF:

0.559

AC:

1945

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 15262185, 19850125, 18178499, 18728290, 20884100) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.85

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over