rs55671147

Positions:

• chr19-50377797-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645

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

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	UniProt
NR1H2	NM_007121.7	c.108G>A	p.Glu36=	synonymous_variant	4/10	ENST00000253727.10
NR1H2	NM_001256647.3	c.108G>A	p.Glu36=	synonymous_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H2	ENST00000253727.10	c.108G>A	p.Glu36=	synonymous_variant	4/10	1	NM_007121.7	P1

Frequencies

GnomAD3 genomes AF: 0.00871 AC: 1325 AN: 152088 Hom.: 12 Cov.: 32

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.: 20 AF XY: 0.00962 AC XY: 1281 AN XY: 133116

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.: 32 AF XY: 0.0140 AC XY: 10152 AN XY: 725594

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.: 12 Cov.: 32 AF XY: 0.00743 AC XY: 553 AN XY: 74412

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.: 12

Bravo AF: 0.00863

Asia WGS AF: 0.00260 AC: 9 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

Other links and lift over

dbSNP: rs55671147; hg19: chr19-50881054; COSMIC: COSV99516635; COSMIC: COSV99516635;