rs1052677

chr19-50382924-C-Gchr19-50382924-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.*322C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 158,234 control chromosomes in the GnomAD database, including 1,769 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 0.45 (1109 hom., cov: 34)
  • Exomes 𝑓: 0.096 (660 hom.)
• Consequence: NR1H2 NM_007121.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.81

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1H2	NM_007121.7	c.*322C>G		3_prime_UTR_variant	10/10	ENST00000253727.10
NR1H2	NM_001256647.3	c.*322C>G		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H2	ENST00000253727.10	c.*322C>G		3_prime_UTR_variant	10/10	1	NM_007121.7	P1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 17251 AN: 38486 Hom.: 1112 Cov.: 34

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.480

GnomAD4 exome AF: 0.0959 AC: 11483 AN: 119734 Hom.: 660 Cov.: 0 AF XY: 0.0969 AC XY: 5792 AN XY: 59790

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.0866

Gnomad4 ASJ exome AF: 0.158

Gnomad4 EAS exome AF: 0.166

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.0436

Gnomad4 NFE exome AF: 0.0834

Gnomad4 OTH exome AF: 0.0995

GnomAD4 genome AF: 0.448 AC: 17250 AN: 38500 Hom.: 1109 Cov.: 34 AF XY: 0.453 AC XY: 8321 AN XY: 18358

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.477

Alfa AF: 0.110 Hom.: 81

Bravo AF: 0.119

Asia WGS AF: 0.176 AC: 599 AN: 3410

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.0070
Dann	Benign	0.29

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: rs1052677; hg19: chr19-50886181; COSMIC: COSV53799824; COSMIC: COSV53799824;