Genetic Variant NR1H2:c.928-119G>C (chr19-50379661-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_007121.7(NR1H2):c.928-119G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 693,124 control chromosomes in the GnomAD database, including 37,138 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 0.30 ( 6962 hom., cov: 32)

Exomes 𝑓: 0.33 ( 30176 hom. )

Consequence

NR1H2
NM_007121.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.636

Publications

9 publications found

Variant links:

Genes affected

NR1H2 (HGNC:7965): (nuclear receptor subfamily 1 group H member 2) The liver X receptors, LXRA (NR1H3; MIM 602423) and LXRB, form a subfamily of the nuclear receptor superfamily and are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. The inducible LXRA is highly expressed in liver, adrenal gland, intestine, adipose tissue, macrophages, lung, and kidney, whereas LXRB is ubiquitously expressed. Ligand-activated LXRs form obligate heterodimers with retinoid X receptors (RXRs; see MIM 180245) and regulate expression of target genes containing LXR response elements (summary by Korf et al., 2009 [PubMed 19436111]).[supplied by OMIM, Jan 2010]

NR1H2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007121.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H2	NM_007121.7	MANE Select	c.928-119G>C		intron	N/A	NP_009052.4	P55055-1
	NR1H2	NM_001256647.3		c.637-119G>C		intron	N/A	NP_001243576.2	P55055-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NR1H2	ENST00000253727.10	TSL:1 MANE Select	c.928-119G>C	intron	N/A	ENSP00000253727.4	P55055-1
NR1H2	ENST00000411902.6	TSL:1	c.637-119G>C	intron	N/A	ENSP00000396151.2	P55055-2
NR1H2	ENST00000967772.1		c.928-119G>C	intron	N/A	ENSP00000637831.1

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

44707

AN:

149372

Hom.:

6960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.374

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.307

GnomAD4 exome

AF:

0.327

AC:

177603

AN:

543644

Hom.:

30176

AF XY:

0.331

AC XY:

95858

AN XY:

290036

show subpopulations

African (AFR)

AF:

0.210

AC:

3338

AN:

15932

American (AMR)

AF:

0.433

AC:

14453

AN:

33354

Ashkenazi Jewish (ASJ)

AF:

0.385

AC:

6946

AN:

18034

East Asian (EAS)

AF:

0.174

AC:

5596

AN:

32134

South Asian (SAS)

AF:

0.366

AC:

21590

AN:

59034

European-Finnish (FIN)

AF:

0.300

AC:

11160

AN:

37172

Middle Eastern (MID)

AF:

0.382

AC:

1484

AN:

3886

European-Non Finnish (NFE)

AF:

0.330

AC:

103652

AN:

314020

Other (OTH)

AF:

0.312

AC:

9384

AN:

30078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

6025

12049

18074

24098

30123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

738

1476

2214

2952

3690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.299

AC:

44726

AN:

149480

Hom.:

6962

Cov.:

AF XY:

0.300

AC XY:

21886

AN XY:

73064

show subpopulations

African (AFR)

AF:

0.217

AC:

8518

AN:

39280

American (AMR)

AF:

0.382

AC:

5786

AN:

15154

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

1342

AN:

3470

East Asian (EAS)

AF:

0.163

AC:

840

AN:

5152

South Asian (SAS)

AF:

0.375

AC:

1760

AN:

4698

European-Finnish (FIN)

AF:

0.296

AC:

3123

AN:

10566

Middle Eastern (MID)

AF:

0.353

AC:

103

AN:

292

European-Non Finnish (NFE)

AF:

0.328

AC:

22279

AN:

67880

Other (OTH)

AF:

0.303

AC:

630

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1618

3237

4855

6474

8092

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.135

Hom.:

274

Bravo

AF:

0.292

Asia WGS

AF:

0.253

AC:

869

AN:

3428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.44

PhyloP100

-0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.37

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.37

Position offset: 26

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over