11-47264739-T-C

Variant names:

• chr11-47264739-T-C
• rs7120118
• NM_005693.4:c.988+2721T>C

Variant summary

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

The NM_005693.4(NR1H3):​c.988+2721T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,060 control chromosomes in the GnomAD database, including 12,001 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 0.38 (12001 hom., cov: 32)
• Consequence: NR1H3 NM_005693.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.749
• Publications: 99 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

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.988+2721T>C		intron	N/A	NP_005684.2	F1D8N1
	NR1H3	NM_001251934.2		c.1006+2721T>C		intron	N/A	NP_001238863.1	B4DXU5
	NR1H3	NM_001251935.2		c.1006+2721T>C		intron	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.988+2721T>C		intron	N/A	ENSP00000387946.2	Q13133-1
	NR1H3	ENST00000616973.4	TSL:1	c.1006+2721T>C		intron	N/A	ENSP00000477707.1	B4DXU5
	NR1H3	ENST00000467728.5	TSL:1	c.988+2721T>C		intron	N/A	ENSP00000420656.1	Q13133-1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57832 AN: 151940 Hom.: 11997 Cov.: 32

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.381 AC: 57866 AN: 152060 Hom.: 12001 Cov.: 32 AF XY: 0.391 AC XY: 29057 AN XY: 74342

African (AFR) AF: 0.480 AC: 19898 AN: 41442

American (AMR) AF: 0.354 AC: 5418 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 779 AN: 3470

East Asian (EAS) AF: 0.746 AC: 3852 AN: 5164

South Asian (SAS) AF: 0.465 AC: 2243 AN: 4822

European-Finnish (FIN) AF: 0.427 AC: 4512 AN: 10578

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.298 AC: 20279 AN: 67984

Other (OTH) AF: 0.326 AC: 689 AN: 2112

Alfa AF: 0.324 Hom.: 37319

Bravo AF: 0.378

Asia WGS AF: 0.545 AC: 1893 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7120118; hg19: chr11-47286290;