chr11-47253513-G-A

Variant names:

• chr11-47253513-G-A
• rs10838681
• ENST00000616973.4:c.61+4649G>A

Variant summary

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

The ENST00000616973.4(NR1H3):​c.61+4649G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,000 control chromosomes in the GnomAD database, including 10,020 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 0.34 (10020 hom., cov: 32)
• Consequence: NR1H3 ENST00000616973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 62 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 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+4649G>A		intron	N/A	NP_001238863.1
	NR1H3	NM_001251935.2		c.61+4649G>A		intron	N/A	NP_001238864.1
	NR1H3	NM_001130102.3		c.-93+4514G>A		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+4649G>A		intron	N/A	ENSP00000477707.1
	NR1H3	ENST00000395397.7	TSL:1	c.-93+4514G>A		intron	N/A	ENSP00000378793.3
	NR1H3	ENST00000527464.5	TSL:1	n.282+4649G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52266 AN: 151880 Hom.: 10013 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.344 AC: 52293 AN: 152000 Hom.: 10020 Cov.: 32 AF XY: 0.353 AC XY: 26198 AN XY: 74308

African (AFR) AF: 0.450 AC: 18627 AN: 41434

American (AMR) AF: 0.337 AC: 5139 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3464

East Asian (EAS) AF: 0.705 AC: 3641 AN: 5164

South Asian (SAS) AF: 0.346 AC: 1668 AN: 4820

European-Finnish (FIN) AF: 0.379 AC: 4009 AN: 10564

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17700 AN: 67972

Other (OTH) AF: 0.291 AC: 614 AN: 2112

Alfa AF: 0.284 Hom.: 28112

Bravo AF: 0.347

Asia WGS AF: 0.426 AC: 1479 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.48
DANN	Benign	0.46
PhyloP100		-0.20
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: rs10838681; hg19: chr11-47275064;