ENST00000616973.4:c.61+2674G>C

Variant names:

• chr11-47251538-G-C
• rs3758671
• ENST00000616973.4:c.61+2674G>C

Variant summary

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

The ENST00000616973.4(NR1H3):​c.61+2674G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,018 control chromosomes in the GnomAD database, including 1,061 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 (1061 hom., cov: 32)
• Consequence: NR1H3 ENST00000616973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 3 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000616973.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H3	NM_001251934.2		c.61+2674G>C		intron	N/A	NP_001238863.1
	NR1H3	NM_001251935.2		c.61+2674G>C		intron	N/A	NP_001238864.1
	NR1H3	NM_001130102.3		c.-93+2539G>C		intron	N/A	NP_001123574.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H3	ENST00000616973.4	TSL:1	c.61+2674G>C		intron	N/A	ENSP00000477707.1
	NR1H3	ENST00000395397.7	TSL:1	c.-93+2539G>C		intron	N/A	ENSP00000378793.3
	NR1H3	ENST00000527464.5	TSL:1	n.282+2674G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16666 AN: 151900 Hom.: 1065 Cov.: 32

Gnomad AFR AF: 0.0546

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.0930

Gnomad EAS AF: 0.0968

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.110 AC: 16659 AN: 152018 Hom.: 1061 Cov.: 32 AF XY: 0.110 AC XY: 8185 AN XY: 74314

African (AFR) AF: 0.0546 AC: 2263 AN: 41472

American (AMR) AF: 0.0783 AC: 1196 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0930 AC: 323 AN: 3472

East Asian (EAS) AF: 0.0960 AC: 496 AN: 5164

South Asian (SAS) AF: 0.229 AC: 1102 AN: 4812

European-Finnish (FIN) AF: 0.130 AC: 1378 AN: 10564

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9607 AN: 67946

Other (OTH) AF: 0.104 AC: 219 AN: 2110

Alfa AF: 0.0677 Hom.: 91

Bravo AF: 0.0991

Asia WGS AF: 0.195 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.53
PhyloP100		0.084
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: rs3758671; hg19: chr11-47273089;