rs4802703

chr19-50381628-C-Achr19-50381628-C-G

Variant summary

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

The NM_007121.7(NR1H2):c.1028-338C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,128 control chromosomes in the GnomAD database, including 5,847 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 0.27 (5847 hom., cov: 33)
• Consequence: NR1H2 NM_007121.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1H2	NM_007121.7	c.1028-338C>A		intron_variant		ENST00000253727.10
NR1H2	NM_001256647.3	c.737-338C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H2	ENST00000253727.10	c.1028-338C>A		intron_variant		1	NM_007121.7	P1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40558 AN: 152010 Hom.: 5843 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.279

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.267 AC: 40579 AN: 152128 Hom.: 5847 Cov.: 33 AF XY: 0.265 AC XY: 19711 AN XY: 74384

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.276

Alfa AF: 0.289 Hom.: 6646

Bravo AF: 0.267

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	3.4
Dann	Benign	0.75

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: rs4802703; hg19: chr19-50884885;