Variant 12-100503453-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000551379.5(NR1H4):c.66G>A(p.Pro22=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00454 in 1,597,418 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 61 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 83 hom. )

Consequence

NR1H4
ENST00000551379.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.23

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 12-100503453-G-A is Benign according to our data. Variant chr12-100503453-G-A is described in ClinVar as [Benign]. Clinvar id is 1271831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 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.80-7325G>A		intron_variant		ENST00000392986.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H4	ENST00000392986.8 linkuse as main transcript	c.80-7325G>A		intron_variant		1	NM_001206979.2	A1	Q96RI1-1

Frequencies

GnomAD3 genomes

AF:

0.0175

AC:

2661

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0543

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00148

Gnomad OTH

AF:

0.0138

GnomAD3 exomes

AF:

0.00645

AC:

1474

AN:

228372

Hom.:

AF XY:

0.00556

AC XY:

702

AN XY:

126200

show subpopulations

Gnomad AFR exome

AF:

0.0548

Gnomad AMR exome

AF:

0.00672

Gnomad ASJ exome

AF:

0.0225

Gnomad EAS exome

AF:

0.000171

Gnomad SAS exome

AF:

0.000597

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00175

Gnomad OTH exome

AF:

0.00960

GnomAD4 exome

AF:

0.00317

AC:

4583

AN:

1445186

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

2186

AN XY:

719252

show subpopulations

Gnomad4 AFR exome

AF:

0.0601

Gnomad4 AMR exome

AF:

0.00829

Gnomad4 ASJ exome

AF:

0.0220

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000476

Gnomad4 FIN exome

AF:

0.0000263

Gnomad4 NFE exome

AF:

0.000970

Gnomad4 OTH exome

AF:

0.00722

GnomAD4 genome

AF:

0.0175

AC:

2665

AN:

152232

Hom.:

Cov.:

AF XY:

0.0167

AC XY:

1241

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0543

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.0231

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00148

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00611

Hom.:

Bravo

AF:

0.0208

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00224

EpiControl

AF:

0.00262

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	Jun 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0010

DANN

Benign

0.53

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