rs11039149

Variant names:

• chr11-47255124-A-G
• rs11039149
• ENST00000616973.4:c.62-4667A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000616973.4(NR1H3):​c.62-4667A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,190 control chromosomes in the GnomAD database, including 3,499 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 0.19 (3499 hom., cov: 32)
• Consequence: NR1H3 ENST00000616973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• Publications: 42 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1H3	NM_001251934.2	c.62-4667A>G		intron_variant	Intron 2 of 9		NP_001238863.1
NR1H3	NM_001251935.2	c.62-4667A>G		intron_variant	Intron 2 of 9		NP_001238864.1
NR1H3	NM_001130102.3	c.-92-4667A>G		intron_variant	Intron 1 of 8		NP_001123574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1H3	ENST00000616973.4	c.62-4667A>G		intron_variant	Intron 2 of 9	1		ENSP00000477707.1
NR1H3	ENST00000395397.7	c.-92-4667A>G		intron_variant	Intron 1 of 8	1		ENSP00000378793.3
NR1H3	ENST00000527464.5	n.283-4667A>G		intron_variant	Intron 2 of 6	1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28360 AN: 152072 Hom.: 3500 Cov.: 32

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.186 AC: 28356 AN: 152190 Hom.: 3499 Cov.: 32 AF XY: 0.181 AC XY: 13462 AN XY: 74400

African (AFR) AF: 0.0467 AC: 1941 AN: 41548

American (AMR) AF: 0.185 AC: 2828 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3466

East Asian (EAS) AF: 0.0210 AC: 109 AN: 5184

South Asian (SAS) AF: 0.195 AC: 939 AN: 4820

European-Finnish (FIN) AF: 0.178 AC: 1884 AN: 10586

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18947 AN: 67980

Other (OTH) AF: 0.222 AC: 468 AN: 2112

Alfa AF: 0.241 Hom.: 10276

Bravo AF: 0.179

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.54
DANN	Benign	0.73
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11039149; hg19: chr11-47276675;