Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_005693.4(NR1H3):c.213G>A(p.Glu71Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,396,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
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]
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
31194
American (AMR)
AF:
0.00
AC:
0
AN:
33350
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21800
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38820
South Asian (SAS)
AF:
0.0000132
AC:
1
AN:
75734
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
50672
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5414
European-Non Finnish (NFE)
AF:
9.24e-7
AC:
1
AN:
1081810
Other (OTH)
AF:
0.00
AC:
0
AN:
57332
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.044843), which strongly suggests a high chance of mosaicism in these individuals.