19-50379362-T-C

Variant summary

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

The NM_007121.7(NR1H2):c.927+181T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,068 control chromosomes in the GnomAD database, including 11,680 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 0.38 (11680 hom., cov: 33)
• Consequence: NR1H2 NM_007121.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.57

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1H2	NM_007121.7	c.927+181T>C		intron_variant		ENST00000253727.10
NR1H2	NM_001256647.3	c.636+181T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H2	ENST00000253727.10	c.927+181T>C		intron_variant		1	NM_007121.7	P1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57767 AN: 151950 Hom.: 11651 Cov.: 33

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.379

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.381 AC: 57863 AN: 152068 Hom.: 11680 Cov.: 33 AF XY: 0.379 AC XY: 28164 AN XY: 74312

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.362

Alfa AF: 0.343 Hom.: 12340

Bravo AF: 0.390

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.10
Dann	Benign	0.33

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: rs1405655; hg19: chr19-50882619; COSMIC: COSV53802741; COSMIC: COSV53802741;