dbSNP rs17373080: NR1H2:c.-127-452C>G (chr19-50376267-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000600355.5(NR1H2):c.-127-452C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,252 control chromosomes in the GnomAD database, including 6,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6931 hom., cov: 33)

Exomes 𝑓: 0.27 ( 0 hom. )

Consequence

NR1H2
ENST00000600355.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.23

Publications

18 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 19-50376267-C-G is Benign according to our data. Variant chr19-50376267-C-G is described in ClinVar as Benign. ClinVar VariationId is 1263505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000600355.5. 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.-437C>G		upstream_gene	N/A	NP_009052.4	P55055-1
	NR1H2	NM_001256647.3		c.-437C>G		upstream_gene	N/A	NP_001243576.2	P55055-2

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
NR1H2	ENST00000652203.1	c.-127-452C>G	intron	N/A	ENSP00000499121.1	P55055-1
NR1H2	ENST00000939061.1	c.-127-452C>G	intron	N/A	ENSP00000609120.1
NR1H2	ENST00000939062.1	c.-127-452C>G	intron	N/A	ENSP00000609121.1

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44631

AN:

152112

Hom.:

6929

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.387

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.351

Gnomad FIN

AF:

0.296

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.299

GnomAD4 exome

AF:

0.273

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.293

AC:

44651

AN:

152230

Hom.:

6931

Cov.:

AF XY:

0.294

AC XY:

21853

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.205

AC:

8499

AN:

41548

American (AMR)

AF:

0.379

AC:

5794

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

1341

AN:

3466

East Asian (EAS)

AF:

0.162

AC:

840

AN:

5176

South Asian (SAS)

AF:

0.352

AC:

1699

AN:

4828

European-Finnish (FIN)

AF:

0.296

AC:

3133

AN:

10588

Middle Eastern (MID)

AF:

0.353

AC:

103

AN:

292

European-Non Finnish (NFE)

AF:

0.327

AC:

22274

AN:

68022

Other (OTH)

AF:

0.296

AC:

625

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1665

3329

4994

6658

8323

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:

0.309

Hom.:

938

Bravo

AF:

0.292

Asia WGS

AF:

0.247

AC:

858

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

5.9

(source)

DANN

Benign

0.66

PhyloP100

1.2

PromoterAI

0.00030

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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