11-47259814-CCA-ACT

Variant names:

• chr11-47259814-CCA-ACT
• NM_005693.4:c.67_69delCCAinsACT
• NR1H3 p.Pro23Thr

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005693.4(NR1H3):​c.67_69delCCAinsACT​(p.Pro23Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NR1H3 NM_005693.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005693.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H3	NM_005693.4	MANE Select	c.67_69delCCAinsACT	p.Pro23Thr	missense	N/A	NP_005684.2	F1D8N1
	NR1H3	NM_001251934.2		c.85_87delCCAinsACT	p.Pro29Thr	missense	N/A	NP_001238863.1	B4DXU5
	NR1H3	NM_001251935.2		c.85_87delCCAinsACT	p.Pro29Thr	missense	N/A	NP_001238864.1	B4DXU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H3	ENST00000441012.7	TSL:1 MANE Select	c.67_69delCCAinsACT	p.Pro23Thr	missense	N/A	ENSP00000387946.2	Q13133-1
	NR1H3	ENST00000616973.4	TSL:1	c.85_87delCCAinsACT	p.Pro29Thr	missense	N/A	ENSP00000477707.1	B4DXU5
	NR1H3	ENST00000467728.5	TSL:1	c.67_69delCCAinsACT	p.Pro23Thr	missense	N/A	ENSP00000420656.1	Q13133-1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-47281365;