rs11039155

Positions:

• chr11-47259211-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_005693.4(NR1H3):​c.-6G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,956 control chromosomes in the GnomAD database, including 19,103 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 0.12 (1470 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17633 hom.)
• Consequence: NR1H3 NM_005693.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

Genes affected

NR1H3 (HGNC:7966): (nuclear receptor subfamily 1 group H member 3) The protein encoded by this gene belongs to the NR1 subfamily of the nuclear receptor superfamily. The NR1 family members are key regulators of macrophage function, controlling transcriptional programs involved in lipid homeostasis and inflammation. This protein is highly expressed in visceral organs, including liver, kidney and intestine. It forms a heterodimer with retinoid X receptor (RXR), and regulates expression of target genes containing retinoid response elements. Studies in mice lacking this gene suggest that it may play an important role in the regulation of cholesterol homeostasis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

NR1H3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1H3	NM_005693.4	c.-6G>A		5_prime_UTR_variant	2/10	ENST00000441012.7	NP_005684.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1H3	ENST00000441012	c.-6G>A		5_prime_UTR_variant	2/10	1	NM_005693.4	ENSP00000387946.2

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17793 AN: 152066 Hom.: 1469 Cov.: 32

Gnomad AFR AF: 0.0270

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00557

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.0938

GnomAD3 exomes AF: 0.138 AC: 34597 AN: 251490 Hom.: 3026 AF XY: 0.144 AC XY: 19521 AN XY: 135920

Gnomad AFR exome AF: 0.0254

Gnomad AMR exome AF: 0.121

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.00163

Gnomad SAS exome AF: 0.194

Gnomad FIN exome AF: 0.268

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.148 AC: 215765 AN: 1461772 Hom.: 17633 Cov.: 33 AF XY: 0.149 AC XY: 108534 AN XY: 727196

Gnomad4 AFR exome AF: 0.0216

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.00229

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.117 AC: 17797 AN: 152184 Hom.: 1470 Cov.: 32 AF XY: 0.124 AC XY: 9237 AN XY: 74378

Gnomad4 AFR AF: 0.0269

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00559

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.0919

Alfa AF: 0.129 Hom.: 1610

Bravo AF: 0.0983

Asia WGS AF: 0.0730 AC: 253 AN: 3478

EpiCase AF: 0.137

EpiControl AF: 0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.92

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: rs11039155; hg19: chr11-47280762;