rs12972221

chr19-50375883-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000652203.1(NR1H2):c.-127-836G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,000 control chromosomes in the GnomAD database, including 6,923 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 0.29 (6923 hom., cov: 33)
• Consequence: NR1H2 ENST00000652203.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H2	ENST00000600355.5	c.-127-836G>T		intron_variant		3
NR1H2	ENST00000652203.1	c.-127-836G>T		intron_variant				P1
NR1H2	ENST00000593532.5	c.-469-352G>T		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44618 AN: 151892 Hom.: 6921 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44640 AN: 152000 Hom.: 6923 Cov.: 33 AF XY: 0.294 AC XY: 21849 AN XY: 74298

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.298

Alfa AF: 0.310 Hom.: 945

Bravo AF: 0.292

Asia WGS AF: 0.249 AC: 866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12972221; hg19: chr19-50879140;