rs41432149

Positions:

• chr19-50378915-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.748-87C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,545,210 control chromosomes in the GnomAD database, including 82,696 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 0.29 (6944 hom., cov: 32)
  • Exomes 𝑓: 0.33 (75752 hom.)
• Consequence: NR1H2 NM_007121.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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]

NR1H2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1H2	NM_007121.7	c.748-87C>T		intron_variant		ENST00000253727.10	NP_009052.4
NR1H2	NM_001256647.3	c.457-87C>T		intron_variant			NP_001243576.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1H2	ENST00000253727.10	c.748-87C>T		intron_variant		1	NM_007121.7	ENSP00000253727.4

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44743 AN: 151852 Hom.: 6942 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.326 AC: 454267 AN: 1393240 Hom.: 75752 Cov.: 31 AF XY: 0.328 AC XY: 224923 AN XY: 686190

Gnomad4 AFR exome AF: 0.203

Gnomad4 AMR exome AF: 0.438

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.305

Gnomad4 NFE exome AF: 0.329

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.295 AC: 44764 AN: 151970 Hom.: 6944 Cov.: 32 AF XY: 0.295 AC XY: 21917 AN XY: 74292

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.298

Alfa AF: 0.311 Hom.: 952

Bravo AF: 0.293

Asia WGS AF: 0.251 AC: 872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.68

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: rs41432149; hg19: chr19-50882172; COSMIC: COSV53801117; COSMIC: COSV53801117;