chr19-50379661-G-C

Position:

• chr19-50379661-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000253727.10(NR1H2):​c.928-119G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 693,124 control chromosomes in the GnomAD database, including 37,138 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 0.30 (6962 hom., cov: 32)
  • Exomes 𝑓: 0.33 (30176 hom.)
• Consequence: NR1H2 ENST00000253727.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1H2	NM_007121.7	c.928-119G>C		intron_variant		ENST00000253727.10	NP_009052.4
NR1H2	NM_001256647.3	c.637-119G>C		intron_variant			NP_001243576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1H2	ENST00000253727.10	c.928-119G>C		intron_variant		1	NM_007121.7	ENSP00000253727	P1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 44707 AN: 149372 Hom.: 6960 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.327 AC: 177603 AN: 543644 Hom.: 30176 AF XY: 0.331 AC XY: 95858 AN XY: 290036

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.433

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.330

Gnomad4 OTH exome AF: 0.312

GnomAD4 genome AF: 0.299 AC: 44726 AN: 149480 Hom.: 6962 Cov.: 32 AF XY: 0.300 AC XY: 21886 AN XY: 73064

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.375

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.303

Alfa AF: 0.135 Hom.: 274

Bravo AF: 0.292

Asia WGS AF: 0.253 AC: 869 AN: 3428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.37		Position offset: 26

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

Publications

LitVar

Other links and lift over

dbSNP: rs2303045; hg19: chr19-50882918; COSMIC: COSV53802390; COSMIC: COSV53802390;