rs6686001

Variant names:

• chr1-161236108-G-A
• rs6686001
• NM_005122.5:c.108-131C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-161236108-G-A
• chr1-161236108-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005122.5(NR1I3):​c.108-131C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000481 in 894,254 control chromosomes in the GnomAD database, including 2 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: not found (cov: 31)
  • Exomes 𝑓: 0.000048 (2 hom.)
• Consequence: NR1I3 NM_005122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• Publications: 7 publications found

Genes affected

NR1I3 (HGNC:7969): (nuclear receptor subfamily 1 group I member 3) This gene encodes a member of the nuclear receptor superfamily, and is a key regulator of xenobiotic and endobiotic metabolism. The protein binds to DNA as a monomer or a heterodimer with the retinoid X receptor and regulates the transcription of target genes involved in drug metabolism and bilirubin clearance, such as cytochrome P450 family members. Unlike most nuclear receptors, this transcriptional regulator is constitutively active in the absence of ligand but is regulated by both agonists and inverse agonists. Ligand binding results in translocation of this protein to the nucleus, where it activates or represses target gene transcription. These ligands include bilirubin, a variety of foreign compounds, steroid hormones, and prescription drugs. In addition to drug metabolism, the CAR protein is also reported to regulate genes involved in glucose metabolism, lipid metabolism, cell proliferation, and circadian clock regulation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2020]

NR1I3 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAdExome4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I3	NM_005122.5	c.108-131C>T		intron_variant	Intron 2 of 8	ENST00000367983.9	NP_005113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I3	ENST00000367983.9	c.108-131C>T		intron_variant	Intron 2 of 8	1	NM_005122.5	ENSP00000356962.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000481 AC: 43 AN: 894254 Hom.: 2 Cov.: 12 AF XY: 0.0000713 AC XY: 32 AN XY: 448928

African (AFR) AF: 0.00 AC: 0 AN: 20682

American (AMR) AF: 0.00 AC: 0 AN: 19766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16402

East Asian (EAS) AF: 0.00 AC: 0 AN: 33758

South Asian (SAS) AF: 0.000757 AC: 42 AN: 55456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3858

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 661486

Other (OTH) AF: 0.0000246 AC: 1 AN: 40720

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.63
PhyloP100		-0.42
PromoterAI		-0.031	Neutral

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: rs6686001; hg19: chr1-161205898;