Variant rs2162459 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000780.4(CYP7A1):c.81-14C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,612,524 control chromosomes in the GnomAD database, including 267,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 22119 hom., cov: 32)

Exomes 𝑓: 0.58 ( 245415 hom. )

Consequence

CYP7A1
NM_000780.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.35

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 8-58498483-G-A is Benign according to our data. Variant chr8-58498483-G-A is described in ClinVar as [Benign]. Clinvar id is 1244824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-58498483-G-A is described in Lovd as [Benign].

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	Protein	UniProt
CYP7A1	NM_000780.4 linkuse as main transcript	c.81-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000301645.4	NP_000771.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP7A1	ENST00000301645.4 linkuse as main transcript	c.81-14C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000780.4	ENSP00000301645	P1

Frequencies

GnomAD3 genomes

AF:

0.532

AC:

80756

AN:

151888

Hom.:

22098

Cov.:

show subpopulations

Gnomad AFR

AF:

0.414

Gnomad AMI

AF:

0.604

Gnomad AMR

AF:

0.653

Gnomad ASJ

AF:

0.642

Gnomad EAS

AF:

0.431

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

GnomAD3 exomes

AF:

0.562

AC:

140940

AN:

250832

Hom.:

40795

AF XY:

0.557

AC XY:

75592

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.412

Gnomad AMR exome

AF:

0.717

Gnomad ASJ exome

AF:

0.634

Gnomad EAS exome

AF:

0.438

Gnomad SAS exome

AF:

0.491

Gnomad FIN exome

AF:

0.493

Gnomad NFE exome

AF:

0.581

Gnomad OTH exome

AF:

0.583

GnomAD4 exome

AF:

0.576

AC:

841650

AN:

1460518

Hom.:

245415

Cov.:

AF XY:

0.573

AC XY:

416029

AN XY:

726576

show subpopulations

Gnomad4 AFR exome

AF:

0.407

Gnomad4 AMR exome

AF:

0.711

Gnomad4 ASJ exome

AF:

0.638

Gnomad4 EAS exome

AF:

0.432

Gnomad4 SAS exome

AF:

0.493

Gnomad4 FIN exome

AF:

0.501

Gnomad4 NFE exome

AF:

0.590

Gnomad4 OTH exome

AF:

0.574

GnomAD4 genome

AF:

0.532

AC:

80808

AN:

152006

Hom.:

22119

Cov.:

AF XY:

0.528

AC XY:

39245

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.413

Gnomad4 AMR

AF:

0.654

Gnomad4 ASJ

AF:

0.642

Gnomad4 EAS

AF:

0.431

Gnomad4 SAS

AF:

0.506

Gnomad4 FIN

AF:

0.486

Gnomad4 NFE

AF:

0.585

Gnomad4 OTH

AF:

0.561

Alfa

AF:

0.577

Hom.:

34521

Bravo

AF:

0.539

Asia WGS

AF:

0.514

AC:

1787

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.59

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

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