ENST00000616973.4:c.62-2404T>C

Variant names:

• chr11-47257387-T-C
• rs3758674
• ENST00000616973.4:c.62-2404T>C

Variant summary

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

The ENST00000616973.4(NR1H3):​c.62-2404T>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 152,174 control chromosomes in the GnomAD database, including 1,069 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 (1069 hom., cov: 31)
• Consequence: NR1H3 ENST00000616973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 24 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H3	NM_001251934.2		c.62-2404T>C		intron	N/A	NP_001238863.1	B4DXU5
	NR1H3	NM_001251935.2		c.62-2404T>C		intron	N/A	NP_001238864.1	B4DXU5
	NR1H3	NM_001130102.3		c.-92-2404T>C		intron	N/A	NP_001123574.1	Q13133-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H3	ENST00000616973.4	TSL:1	c.62-2404T>C		intron	N/A	ENSP00000477707.1	B4DXU5
	NR1H3	ENST00000395397.7	TSL:1	c.-92-2404T>C		intron	N/A	ENSP00000378793.3	Q13133-3
	NR1H3	ENST00000527464.5	TSL:1	n.283-2404T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16794 AN: 152056 Hom.: 1073 Cov.: 31

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0786

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.110 AC: 16787 AN: 152174 Hom.: 1069 Cov.: 31 AF XY: 0.111 AC XY: 8252 AN XY: 74406

African (AFR) AF: 0.0574 AC: 2383 AN: 41520

American (AMR) AF: 0.0784 AC: 1200 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3470

East Asian (EAS) AF: 0.0956 AC: 494 AN: 5170

South Asian (SAS) AF: 0.229 AC: 1102 AN: 4820

European-Finnish (FIN) AF: 0.131 AC: 1389 AN: 10598

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.141 AC: 9602 AN: 67972

Other (OTH) AF: 0.104 AC: 221 AN: 2116

Alfa AF: 0.126 Hom.: 1079

Bravo AF: 0.0999

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.70
PhyloP100		-0.072
PromoterAI		0.0041	Neutral
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: rs3758674; hg19: chr11-47278938;