Variant 12-100493323-G-T 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.-1G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0329 in 1,528,466 control chromosomes in the GnomAD database, including 2,047 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 160 hom., cov: 32)

Exomes 𝑓: 0.033 ( 1887 hom. )

Consequence

NR1H4
NM_001206979.2 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.00500

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:

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=-0.58).

BP6

Variant 12-100493323-G-T is Benign according to our data. Variant chr12-100493323-G-T is described in ClinVar as [Benign]. Clinvar id is 259641.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1H4	NM_001206979.2 linkuse as main transcript	c.-1G>T		5_prime_UTR_variant	3/11	ENST00000392986.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H4	ENST00000392986.8 linkuse as main transcript	c.-1G>T		5_prime_UTR_variant	3/11	1	NM_001206979.2	A1	Q96RI1-1

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

4694

AN:

152062

Hom.:

161

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0242

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.0519

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.0222

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0228

Gnomad OTH

AF:

0.0253

GnomAD3 exomes

AF:

0.0466

AC:

10444

AN:

224202

Hom.:

454

AF XY:

0.0499

AC XY:

6011

AN XY:

120418

show subpopulations

Gnomad AFR exome

AF:

0.0258

Gnomad AMR exome

AF:

0.0398

Gnomad ASJ exome

AF:

0.0468

Gnomad EAS exome

AF:

0.137

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.0215

Gnomad NFE exome

AF:

0.0231

Gnomad OTH exome

AF:

0.0377

GnomAD4 exome

AF:

0.0331

AC:

45592

AN:

1376286

Hom.:

1887

Cov.:

AF XY:

0.0354

AC XY:

24356

AN XY:

687218

show subpopulations

Gnomad4 AFR exome

AF:

0.0257

Gnomad4 AMR exome

AF:

0.0367

Gnomad4 ASJ exome

AF:

0.0472

Gnomad4 EAS exome

AF:

0.203

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.0217

Gnomad4 NFE exome

AF:

0.0211

Gnomad4 OTH exome

AF:

0.0340

GnomAD4 genome

AF:

0.0308

AC:

4692

AN:

152180

Hom.:

160

Cov.:

AF XY:

0.0325

AC XY:

2416

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0242

Gnomad4 AMR

AF:

0.0221

Gnomad4 ASJ

AF:

0.0519

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.116

Gnomad4 FIN

AF:

0.0222

Gnomad4 NFE

AF:

0.0228

Gnomad4 OTH

AF:

0.0250

Alfa

AF:

0.0275

Hom.:

Bravo

AF:

0.0304

Asia WGS

AF:

0.104

AC:

360

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 04, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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