Variant rs55671147 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_007121.7(NR1H2):c.108G>A(p.Glu36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,610,756 control chromosomes in the GnomAD database, including 154 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 0.0087 ( 12 hom., cov: 32)

Exomes 𝑓: 0.014 ( 142 hom. )

Consequence

NR1H2
NM_007121.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.645

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP7

Synonymous conserved (PhyloP=0.645 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00871 (1325/152206) while in subpopulation NFE AF= 0.0164 (1113/67984). AF 95% confidence interval is 0.0156. There are 12 homozygotes in gnomad4. There are 553 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1325 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1H2	NM_007121.7 linkuse as main transcript	c.108G>A	p.Glu36=	synonymous_variant	4/10	ENST00000253727.10	NP_009052.4
NR1H2	NM_001256647.3 linkuse as main transcript	c.108G>A	p.Glu36=	synonymous_variant	4/9		NP_001243576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1H2	ENST00000253727.10 linkuse as main transcript	c.108G>A	p.Glu36=	synonymous_variant	4/10	1	NM_007121.7	ENSP00000253727	P1	P55055-1

Frequencies

GnomAD3 genomes

AF:

0.00871

AC:

1325

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0164

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00943

AC:

2309

AN:

244940

Hom.:

AF XY:

0.00962

AC XY:

1281

AN XY:

133116

show subpopulations

Gnomad AFR exome

AF:

0.00176

Gnomad AMR exome

AF:

0.00393

Gnomad ASJ exome

AF:

0.00133

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00704

Gnomad FIN exome

AF:

0.00469

Gnomad NFE exome

AF:

0.0159

Gnomad OTH exome

AF:

0.00933

GnomAD4 exome

AF:

0.0142

AC:

20652

AN:

1458550

Hom.:

142

Cov.:

AF XY:

0.0140

AC XY:

10152

AN XY:

725594

show subpopulations

Gnomad4 AFR exome

AF:

0.00177

Gnomad4 AMR exome

AF:

0.00421

Gnomad4 ASJ exome

AF:

0.00143

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00672

Gnomad4 FIN exome

AF:

0.00562

Gnomad4 NFE exome

AF:

0.0169

Gnomad4 OTH exome

AF:

0.0119

GnomAD4 genome

AF:

0.00871

AC:

1325

AN:

152206

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

553

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.0164

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.0149

Hom.:

Bravo

AF:

0.00863

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

6.6

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over