rs61896015

Variant names:

• chr11-47258377-C-A
• rs61896015
• ENST00000467728.5:c.-840C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-47258377-C-A
• chr11-47258377-C-G
• chr11-47258377-C-T

Variant summary

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

The ENST00000467728.5(NR1H3):​c.-840C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 191,796 control chromosomes in the GnomAD database, including 1,443 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 (1078 hom., cov: 30)
  • Exomes 𝑓: 0.13 (365 hom.)
• Consequence: NR1H3 ENST00000467728.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 9 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=-0.79).
• 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: ENST00000467728.5. 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.-38+248C>A		intron	N/A	NP_005684.2
	NR1H3	NM_001251934.2		c.62-1414C>A		intron	N/A	NP_001238863.1
	NR1H3	NM_001251935.2		c.62-1414C>A		intron	N/A	NP_001238864.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR1H3	ENST00000467728.5	TSL:1	c.-840C>A		5_prime_UTR	Exon 1 of 9	ENSP00000420656.1
	NR1H3	ENST00000441012.7	TSL:1 MANE Select	c.-38+248C>A		intron	N/A	ENSP00000387946.2
	NR1H3	ENST00000616973.4	TSL:1	c.62-1414C>A		intron	N/A	ENSP00000477707.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16792 AN: 151856 Hom.: 1082 Cov.: 30

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.0965

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.131 AC: 5208 AN: 39822 Hom.: 365 Cov.: 4 AF XY: 0.132 AC XY: 2566 AN XY: 19448

African (AFR) AF: 0.0471 AC: 34 AN: 722

American (AMR) AF: 0.00 AC: 0 AN: 46

Ashkenazi Jewish (ASJ) AF: 0.0691 AC: 17 AN: 246

East Asian (EAS) AF: 0.114 AC: 19 AN: 166

South Asian (SAS) AF: 0.215 AC: 177 AN: 824

European-Finnish (FIN) AF: 0.146 AC: 7 AN: 48

Middle Eastern (MID) AF: 0.103 AC: 8 AN: 78

European-Non Finnish (NFE) AF: 0.131 AC: 4784 AN: 36406

Other (OTH) AF: 0.126 AC: 162 AN: 1286

GnomAD4 genome AF: 0.110 AC: 16785 AN: 151974 Hom.: 1078 Cov.: 30 AF XY: 0.111 AC XY: 8245 AN XY: 74250

African (AFR) AF: 0.0575 AC: 2380 AN: 41410

American (AMR) AF: 0.0785 AC: 1198 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3468

East Asian (EAS) AF: 0.0958 AC: 495 AN: 5168

South Asian (SAS) AF: 0.229 AC: 1100 AN: 4806

European-Finnish (FIN) AF: 0.131 AC: 1385 AN: 10558

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

European-Non Finnish (NFE) AF: 0.141 AC: 9609 AN: 67982

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.0606 Hom.: 81

Bravo AF: 0.0999

Asia WGS AF: 0.195 AC: 676 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.1
DANN	Benign	0.46
PhyloP100		0.019
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs61896015; hg19: chr11-47279928;