Genetic Variant NR1H3:c.61+2674G>C (chr11-47251538-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001251934.2(NR1H3):c.61+2674G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,018 control chromosomes in the GnomAD database, including 1,061 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.11 ( 1061 hom., cov: 32)

Consequence

NR1H3
NM_001251934.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0840

Publications

3 publications found

Variant links:

Genes affected

NR1H3 (HGNC:7966): (nuclear receptor subfamily 1 group H member 3) The protein encoded by this gene belongs to the NR1 subfamily of the nuclear receptor superfamily. The NR1 family members are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. This protein is highly expressed in visceral organs, including liver, kidney and intestine. It forms a heterodimer with retinoid X receptor (RXR), and regulates expression of target genes containing retinoid response elements. Studies in mice lacking this gene suggest that it may play an important role in the regulation of cholesterol homeostasis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

NR1H3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001251934.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
NR1H3	NM_001251934.2	c.61+2674G>C	intron	N/A	NP_001238863.1	B4DXU5
NR1H3	NM_001251935.2	c.61+2674G>C	intron	N/A	NP_001238864.1	B4DXU5
NR1H3	NM_001130102.3	c.-93+2539G>C	intron	N/A	NP_001123574.1	Q13133-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NR1H3	ENST00000616973.4	TSL:1	c.61+2674G>C	intron	N/A	ENSP00000477707.1	B4DXU5
NR1H3	ENST00000395397.7	TSL:1	c.-93+2539G>C	intron	N/A	ENSP00000378793.3	Q13133-3
NR1H3	ENST00000527464.5	TSL:1	n.282+2674G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16666

AN:

151900

Hom.:

1065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0546

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0785

Gnomad ASJ

AF:

0.0930

Gnomad EAS

AF:

0.0968

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.104

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.110

AC:

16659

AN:

152018

Hom.:

1061

Cov.:

AF XY:

0.110

AC XY:

8185

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.0546

AC:

2263

AN:

41472

American (AMR)

AF:

0.0783

AC:

1196

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0930

AC:

323

AN:

3472

East Asian (EAS)

AF:

0.0960

AC:

496

AN:

5164

South Asian (SAS)

AF:

0.229

AC:

1102

AN:

4812

European-Finnish (FIN)

AF:

0.130

AC:

1378

AN:

10564

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9607

AN:

67946

Other (OTH)

AF:

0.104

AC:

219

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

757

1513

2270

3026

3783

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0677

Hom.:

Bravo

AF:

0.0991

Asia WGS

AF:

0.195

AC:

676

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.2

(source)

DANN

Benign

0.53

PhyloP100

0.084

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over