19-50381944-C-T

Position:

• chr19-50381944-C-T

Variant summary

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

The NM_007121.7(NR1H2):​c.1028-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 1,536,420 control chromosomes in the GnomAD database, including 5,970 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 0.086 (661 hom., cov: 33)
  • Exomes 𝑓: 0.082 (5309 hom.)
• Consequence: NR1H2 NM_007121.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1H2	NM_007121.7	c.1028-22C>T		intron_variant		ENST00000253727.10	NP_009052.4
NR1H2	NM_001256647.3	c.737-22C>T		intron_variant			NP_001243576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1H2	ENST00000253727.10	c.1028-22C>T		intron_variant		1	NM_007121.7	ENSP00000253727.4

Frequencies

GnomAD3 genomes AF: 0.0864 AC: 13142 AN: 152124 Hom.: 661 Cov.: 33

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0324

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0679

Gnomad OTH AF: 0.0885

GnomAD3 exomes AF: 0.0993 AC: 14400 AN: 145042 Hom.: 862 AF XY: 0.104 AC XY: 8011 AN XY: 76764

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0934

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.132

Gnomad SAS exome AF: 0.170

Gnomad FIN exome AF: 0.0360

Gnomad NFE exome AF: 0.0759

Gnomad OTH exome AF: 0.0958

GnomAD4 exome AF: 0.0816 AC: 112981 AN: 1384178 Hom.: 5309 Cov.: 31 AF XY: 0.0847 AC XY: 57718 AN XY: 681120

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0898

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.170

Gnomad4 FIN exome AF: 0.0362

Gnomad4 NFE exome AF: 0.0715

Gnomad4 OTH exome AF: 0.0881

GnomAD4 genome AF: 0.0863 AC: 13136 AN: 152242 Hom.: 661 Cov.: 33 AF XY: 0.0855 AC XY: 6369 AN XY: 74454

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0784

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.172

Gnomad4 FIN AF: 0.0324

Gnomad4 NFE AF: 0.0680

Gnomad4 OTH AF: 0.0876

Alfa AF: 0.0835 Hom.: 145

Bravo AF: 0.0903

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.046
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2303044; hg19: chr19-50885201; COSMIC: COSV53801972; COSMIC: COSV53801972;