rs78105260

chr19-50379305-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_007121.7(NR1H2):c.927+124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,082,804 control chromosomes in the GnomAD database, including 89 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 0.0091 (13 hom., cov: 33)
  • Exomes 𝑓: 0.010 (76 hom.)
• Consequence: NR1H2 NM_007121.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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=-0.81).
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0103 (9630/930456) while in subpopulation MID AF= 0.0233 (103/4414). AF 95% confidence interval is 0.0197. There are 76 homozygotes in gnomad4_exome. There are 4718 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1394 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1H2	NM_007121.7	c.927+124A>G		intron_variant		ENST00000253727.10
NR1H2	NM_001256647.3	c.636+124A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H2	ENST00000253727.10	c.927+124A>G		intron_variant		1	NM_007121.7	P1

Frequencies

GnomAD3 genomes AF: 0.00916 AC: 1394 AN: 152230 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.00772

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.0103 AC: 9630 AN: 930456 Hom.: 76 AF XY: 0.0101 AC XY: 4718 AN XY: 466424

Gnomad4 AFR exome AF: 0.00157

Gnomad4 AMR exome AF: 0.00994

Gnomad4 ASJ exome AF: 0.0458

Gnomad4 EAS exome AF: 0.0000291

Gnomad4 SAS exome AF: 0.00240

Gnomad4 FIN exome AF: 0.0117

Gnomad4 NFE exome AF: 0.0108

Gnomad4 OTH exome AF: 0.0107

GnomAD4 genome AF: 0.00914 AC: 1392 AN: 152348 Hom.: 13 Cov.: 33 AF XY: 0.00873 AC XY: 650 AN XY: 74498

Gnomad4 AFR AF: 0.00212

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00772

Gnomad4 NFE AF: 0.0119

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0102 Hom.: 0

Bravo AF: 0.00899

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.89
Dann	Benign	0.72

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: rs78105260; hg19: chr19-50882562;