Variant 12-100536435-C-G 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_001206979.2(NR1H4):c.733-77C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 826,604 control chromosomes in the GnomAD database, including 13,702 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1820 hom., cov: 32)

Exomes 𝑓: 0.17 ( 11882 hom. )

Consequence

NR1H4
NM_001206979.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0850

Variant links:

Genes affected

NR1H4 (HGNC:7967): (nuclear receptor subfamily 1 group H member 4) This gene encodes a ligand-activated transcription factor that shares structural features in common with nuclear hormone receptor family members. This protein functions as a receptor for bile acids, and when bound to bile acids, binds to DNA and regulates the expression of genes involved in bile acid synthesis and transport. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Feb 2016]

NR1H4 links:

NR1H4 (HGNC:):

NR1H4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-100536435-C-G is Benign according to our data. Variant chr12-100536435-C-G is described in ClinVar as [Benign]. Clinvar id is 1231661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1H4	NM_001206979.2 linkuse as main transcript	c.733-77C>G		intron_variant		ENST00000392986.8	NP_001193908.1	Q96RI1-1F1DAL1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1H4	ENST00000392986.8 linkuse as main transcript	c.733-77C>G		intron_variant		1	NM_001206979.2	ENSP00000376712.3		Q96RI1-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19700

AN:

151350

Hom.:

1808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0286

Gnomad AMI

AF:

0.0526

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.0955

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.102

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.148

GnomAD4 exome

AF:

0.167

AC:

112624

AN:

675138

Hom.:

11882

AF XY:

0.167

AC XY:

60840

AN XY:

363238

show subpopulations

Gnomad4 AFR exome

AF:

0.0280

Gnomad4 AMR exome

AF:

0.385

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.289

Gnomad4 SAS exome

AF:

0.249

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.130

AC:

19719

AN:

151466

Hom.:

1820

Cov.:

AF XY:

0.138

AC XY:

10186

AN XY:

73962

show subpopulations

Gnomad4 AFR

AF:

0.0285

Gnomad4 AMR

AF:

0.288

Gnomad4 ASJ

AF:

0.0955

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.261

Gnomad4 FIN

AF:

0.173

Gnomad4 NFE

AF:

0.132

Gnomad4 OTH

AF:

0.147

Alfa

AF:

0.0579

Hom.:

Bravo

AF:

0.134

Asia WGS

AF:

0.238

AC:

824

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.94

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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