rs3758674

chr11-47257387-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR1H3	NM_001130102.3	c.-92-2404T>C		intron_variant
NR1H3	NM_001251934.2	c.62-2404T>C		intron_variant
NR1H3	NM_001251935.2	c.62-2404T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR1H3	ENST00000395397.7	c.-92-2404T>C		intron_variant		1
NR1H3	ENST00000616973.4	c.62-2404T>C		intron_variant		1
NR1H3	ENST00000527464.5	n.283-2404T>C		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR AF: 0.0574

Gnomad4 AMR AF: 0.0784

Gnomad4 ASJ AF: 0.0931

Gnomad4 EAS AF: 0.0956

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.104

Alfa AF: 0.133 Hom.: 930

Bravo AF: 0.0999

Asia WGS AF: 0.195 AC: 677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.4
Dann	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3758674; hg19: chr11-47278938;