19-50377484-T-C

Variant names:

• chr19-50377484-T-C
• rs2695121
• ENST00000597157:c.-122T>C

Variant summary

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

The ENST00000597157(NR1H2):​c.-122T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 885,204 control chromosomes in the GnomAD database, including 178,741 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 0.70 (38493 hom., cov: 28)
  • Exomes 𝑓: 0.61 (140248 hom.)
• Consequence: NR1H2 ENST00000597157 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1H2	NM_007121.7	c.-19-103T>C		intron_variant	Intron 2 of 9	ENST00000253727.10	NP_009052.4
NR1H2	NM_001256647.3	c.-19-103T>C		intron_variant	Intron 2 of 8		NP_001243576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1H2	ENST00000253727.10	c.-19-103T>C		intron_variant	Intron 2 of 9	1	NM_007121.7	ENSP00000253727.4

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105198 AN: 151412 Hom.: 38414 Cov.: 28

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.689

GnomAD4 exome AF: 0.611 AC: 448040 AN: 733674 Hom.: 140248 Cov.: 10 AF XY: 0.613 AC XY: 232632 AN XY: 379370

Gnomad4 AFR exome AF: 0.931

Gnomad4 AMR exome AF: 0.655

Gnomad4 ASJ exome AF: 0.736

Gnomad4 EAS exome AF: 0.900

Gnomad4 SAS exome AF: 0.691

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.569

Gnomad4 OTH exome AF: 0.638

GnomAD4 genome AF: 0.695 AC: 105341 AN: 151530 Hom.: 38493 Cov.: 28 AF XY: 0.696 AC XY: 51486 AN XY: 74016

Gnomad4 AFR AF: 0.923

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.875

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.691

Alfa AF: 0.606 Hom.: 7883

Bravo AF: 0.710

Asia WGS AF: 0.789 AC: 2740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.68
DANN	Benign	0.76
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3

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: rs2695121; hg19: chr19-50880741;