dbSNP rs1052677: NR1H2:c.*322C>G (chr19-50382924-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_007121.7(NR1H2):c.*322C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 158,234 control chromosomes in the GnomAD database, including 1,769 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 0.45 ( 1109 hom., cov: 34)

Exomes 𝑓: 0.096 ( 660 hom. )

Consequence

NR1H2
NM_007121.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.81

Publications

7 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:

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=-0.93).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1H2	NM_007121.7 link	c.*322C>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000253727.10	NP_009052.4	P55055-1F1D8P7
NR1H2	NM_001256647.3 link	c.*322C>G		3_prime_UTR_variant	Exon 9 of 9		NP_001243576.2	P55055-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1H2	ENST00000253727.10 link	c.*322C>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_007121.7	ENSP00000253727.4		P55055-1

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

17251

AN:

38486

Hom.:

1112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.496

Gnomad AMI

AF:

0.476

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.362

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.480

GnomAD4 exome

AF:

0.0959

AC:

11483

AN:

119734

Hom.:

660

Cov.:

AF XY:

0.0969

AC XY:

5792

AN XY:

59790

show subpopulations

African (AFR)

AF:

0.137

AC:

566

AN:

4120

American (AMR)

AF:

0.0866

AC:

369

AN:

4260

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

796

AN:

5046

East Asian (EAS)

AF:

0.166

AC:

1749

AN:

10536

South Asian (SAS)

AF:

0.172

AC:

273

AN:

1584

European-Finnish (FIN)

AF:

0.0436

AC:

331

AN:

7592

Middle Eastern (MID)

AF:

0.150

AC:

AN:

654

European-Non Finnish (NFE)

AF:

0.0834

AC:

6455

AN:

77436

Other (OTH)

AF:

0.0995

AC:

846

AN:

8506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

493

986

1478

1971

2464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.448

AC:

17250

AN:

38500

Hom.:

1109

Cov.:

AF XY:

0.453

AC XY:

8321

AN XY:

18358

show subpopulations

African (AFR)

AF:

0.496

AC:

6461

AN:

13022

American (AMR)

AF:

0.448

AC:

1595

AN:

3558

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

604

AN:

1274

East Asian (EAS)

AF:

0.466

AC:

791

AN:

1698

South Asian (SAS)

AF:

0.521

AC:

978

AN:

1876

European-Finnish (FIN)

AF:

0.362

AC:

468

AN:

1292

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.398

AC:

5907

AN:

14848

Other (OTH)

AF:

0.477

AC:

264

AN:

554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

797

1595

2392

3190

3987

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

384

576

768

960

<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:

0.110

Hom.:

Bravo

AF:

0.119

Asia WGS

AF:

0.176

AC:

599

AN:

3410

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.0070

(source)

DANN

Benign

0.29

PhyloP100

-3.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over