rs1052533

Variant names:

• chr19-50378568-G-A
• rs1052533
• NM_007121.7:c.519G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_007121.7(NR1H2):​c.519G>A​(p.Gln173Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000603 in 995,046 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: NR1H2 NM_007121.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.988
• Publications: 14 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.988 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1H2	NM_007121.7	c.519G>A	p.Gln173Gln	synonymous_variant	Exon 6 of 10	ENST00000253727.10	NP_009052.4
NR1H2	NM_001256647.3	c.228G>A	p.Gln76Gln	synonymous_variant	Exon 5 of 9		NP_001243576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1H2	ENST00000253727.10	c.519G>A	p.Gln173Gln	synonymous_variant	Exon 6 of 10	1	NM_007121.7	ENSP00000253727.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000125 AC: 3 AN: 240742 AF XY: 0.00000763

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000183

Gnomad OTH exome AF: 0.000173

GnomAD4 exome AF: 0.00000603 AC: 6 AN: 995046 Hom.: 0 Cov.: 51 AF XY: 0.00000593 AC XY: 3 AN XY: 506050

African (AFR) AF: 0.00 AC: 0 AN: 28336

American (AMR) AF: 0.0000274 AC: 1 AN: 36436

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21372

East Asian (EAS) AF: 0.0000944 AC: 3 AN: 31784

South Asian (SAS) AF: 0.00 AC: 0 AN: 73162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4396

European-Non Finnish (NFE) AF: 0.00000281 AC: 2 AN: 711874

Other (OTH) AF: 0.00 AC: 0 AN: 44082

GnomAD4 genome Cov.: 33

Alfa AF: 0.224 Hom.: 7891

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.2
DANN	Benign	0.71
PhyloP100		0.99
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=296/4	polymorphism

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

Other links and lift over

dbSNP: rs1052533; hg19: chr19-50881825; COSMIC: COSV53800550; COSMIC: COSV53800550;