11-47258377-C-A

Position:

• chr11-47258377-C-A

Variant summary

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

The ENST00000467728.5(NR1H3):​c.-840C>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 0.115 in 191,796 control chromosomes in the GnomAD database, including 1,443 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 0.11 (1078 hom., cov: 30)
  • Exomes 𝑓: 0.13 (365 hom.)
• Consequence: NR1H3 ENST00000467728.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR1H3	NM_005693.4	c.-38+248C>A		intron_variant		ENST00000441012.7	NP_005684.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR1H3	ENST00000441012.7	c.-38+248C>A		intron_variant		1	NM_005693.4	ENSP00000387946	P1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16792 AN: 151856 Hom.: 1082 Cov.: 30

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.0965

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.131 AC: 5208 AN: 39822 Hom.: 365 Cov.: 4 AF XY: 0.132 AC XY: 2566 AN XY: 19448

Gnomad4 AFR exome AF: 0.0471

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0691

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.110 AC: 16785 AN: 151974 Hom.: 1078 Cov.: 30 AF XY: 0.111 AC XY: 8245 AN XY: 74250

Gnomad4 AFR AF: 0.0575

Gnomad4 AMR AF: 0.0785

Gnomad4 ASJ AF: 0.0931

Gnomad4 EAS AF: 0.0958

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0606 Hom.: 76

Bravo AF: 0.0999

Asia WGS AF: 0.195 AC: 676 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.1
DANN	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs61896015; hg19: chr11-47279928;