Variant rs11110413 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001206979.2(NR1H4):c.832-16T>A 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 0.0233 in 1,415,698 control chromosomes in the GnomAD database, including 4,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 2555 hom., cov: 33)

Exomes 𝑓: 0.013 ( 2148 hom. )

Consequence

NR1H4
NM_001206979.2 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.846

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:

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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=-0.26).

BP6

Variant 12-100536932-T-A is Benign according to our data. Variant chr12-100536932-T-A is described in ClinVar as [Benign]. Clinvar id is 259643.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 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.832-16T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000392986.8	NP_001193908.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1H4	ENST00000392986.8 linkuse as main transcript	c.832-16T>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001206979.2	ENSP00000376712	A1	Q96RI1-1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15956

AN:

152070

Hom.:

2540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.350

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0500

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.0156

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00651

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.00375

Gnomad OTH

AF:

0.0746

GnomAD3 exomes

AF:

0.0325

AC:

7149

AN:

220270

Hom.:

983

AF XY:

0.0260

AC XY:

3131

AN XY:

120438

show subpopulations

Gnomad AFR exome

AF:

0.366

Gnomad AMR exome

AF:

0.0266

Gnomad ASJ exome

AF:

0.0343

Gnomad EAS exome

AF:

0.0132

Gnomad SAS exome

AF:

0.00276

Gnomad FIN exome

AF:

0.00546

Gnomad NFE exome

AF:

0.00337

Gnomad OTH exome

AF:

0.0252

GnomAD4 exome

AF:

0.0135

AC:

17005

AN:

1263510

Hom.:

2148

Cov.:

AF XY:

0.0123

AC XY:

7814

AN XY:

637226

show subpopulations

Gnomad4 AFR exome

AF:

0.373

Gnomad4 AMR exome

AF:

0.0306

Gnomad4 ASJ exome

AF:

0.0331

Gnomad4 EAS exome

AF:

0.0107

Gnomad4 SAS exome

AF:

0.00296

Gnomad4 FIN exome

AF:

0.00578

Gnomad4 NFE exome

AF:

0.00200

Gnomad4 OTH exome

AF:

0.0308

GnomAD4 genome

AF:

0.105

AC:

16007

AN:

152188

Hom.:

2555

Cov.:

AF XY:

0.101

AC XY:

7532

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.350

Gnomad4 AMR

AF:

0.0499

Gnomad4 ASJ

AF:

0.0323

Gnomad4 EAS

AF:

0.0156

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.00651

Gnomad4 NFE

AF:

0.00375

Gnomad4 OTH

AF:

0.0743

Alfa

AF:

0.0546

Hom.:

201

Bravo

AF:

0.121

Asia WGS

AF:

0.0520

AC:

178

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 20, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.77

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