19-50376295-C-T

Position:

• chr19-50376295-C-T

Variant summary

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

The ENST00000600355.5(NR1H2):​c.-127-424C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 152,300 control chromosomes in the GnomAD database, including 363 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 0.059 (363 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: NR1H2 ENST00000600355.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.50376295C>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1H2	ENST00000652203.1	c.-127-424C>T		intron_variant				ENSP00000499121.1
NR1H2	ENST00000600355.5	c.-127-424C>T		intron_variant		3		ENSP00000473099.1
NR1H2	ENST00000593532.5	n.-409C>T		non_coding_transcript_exon_variant	5/14	2		ENSP00000472271.1
NR1H2	ENST00000593532.5	n.-409C>T		5_prime_UTR_variant	5/14	2		ENSP00000472271.1

Frequencies

GnomAD3 genomes AF: 0.0590 AC: 8977 AN: 152158 Hom.: 362 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.0567

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00830

Gnomad SAS AF: 0.0884

Gnomad FIN AF: 0.0694

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0790

Gnomad OTH AF: 0.0774

GnomAD4 exome AF: 0.0833 AC: 2 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.0590 AC: 8981 AN: 152276 Hom.: 363 Cov.: 32 AF XY: 0.0593 AC XY: 4416 AN XY: 74460

Gnomad4 AFR AF: 0.0184

Gnomad4 AMR AF: 0.0566

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.00812

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.0694

Gnomad4 NFE AF: 0.0790

Gnomad4 OTH AF: 0.0795

Alfa AF: 0.0606 Hom.: 113

Bravo AF: 0.0557

Asia WGS AF: 0.0440 AC: 152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.7
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56151148; hg19: chr19-50879552;