1-161230796-T-G

Variant names:

• chr1-161230796-T-G
• rs2307418
• NM_005122.5:c.917+17A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005122.5(NR1I3):​c.917+17A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,613,778 control chromosomes in the GnomAD database, including 18,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1253 hom., cov: 31)
  • Exomes 𝑓: 0.15 (17197 hom.)
• Consequence: NR1I3 NM_005122.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.405
• Publications: 30 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]

TOMM40L (HGNC:25756): (translocase of outer mitochondrial membrane 40 like) Predicted to enable protein transmembrane transporter activity. Predicted to be involved in protein import into mitochondrial matrix. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-161230796-T-G is Benign according to our data. Variant chr1-161230796-T-G is described in ClinVar as Benign. ClinVar VariationId is 95259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR1I3	NM_005122.5	c.917+17A>C		intron_variant	Intron 8 of 8	ENST00000367983.9	NP_005113.1
TOMM40L	NM_032174.6	c.*1701T>G		downstream_gene_variant		ENST00000367988.8	NP_115550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR1I3	ENST00000367983.9	c.917+17A>C		intron_variant	Intron 8 of 8	1	NM_005122.5	ENSP00000356962.5
TOMM40L	ENST00000367988.8	c.*1701T>G		downstream_gene_variant		2	NM_032174.6	ENSP00000356967.3

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17490 AN: 152044 Hom.: 1254 Cov.: 31

Gnomad AFR AF: 0.0292

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0878

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.124

GnomAD2 exomes AF: 0.131 AC: 32966 AN: 250878 AF XY: 0.135

Gnomad AFR exome AF: 0.0258

Gnomad AMR exome AF: 0.0878

Gnomad ASJ exome AF: 0.213

Gnomad EAS exome AF: 0.0825

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.156

GnomAD4 exome AF: 0.149 AC: 217248 AN: 1461616 Hom.: 17197 Cov.: 35 AF XY: 0.149 AC XY: 108072 AN XY: 727138

African (AFR) AF: 0.0226 AC: 758 AN: 33480

American (AMR) AF: 0.0898 AC: 4015 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5506 AN: 26136

East Asian (EAS) AF: 0.0746 AC: 2960 AN: 39700

South Asian (SAS) AF: 0.113 AC: 9741 AN: 86254

European-Finnish (FIN) AF: 0.140 AC: 7461 AN: 53208

Middle Eastern (MID) AF: 0.187 AC: 1079 AN: 5768

European-Non Finnish (NFE) AF: 0.159 AC: 176990 AN: 1111958

Other (OTH) AF: 0.145 AC: 8738 AN: 60392

GnomAD4 genome AF: 0.115 AC: 17475 AN: 152162 Hom.: 1253 Cov.: 31 AF XY: 0.114 AC XY: 8458 AN XY: 74370

African (AFR) AF: 0.0292 AC: 1211 AN: 41536

American (AMR) AF: 0.117 AC: 1793 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 696 AN: 3470

East Asian (EAS) AF: 0.0874 AC: 452 AN: 5172

South Asian (SAS) AF: 0.102 AC: 492 AN: 4826

European-Finnish (FIN) AF: 0.141 AC: 1496 AN: 10588

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10932 AN: 67978

Other (OTH) AF: 0.124 AC: 261 AN: 2104

Alfa AF: 0.152 Hom.: 3345

Bravo AF: 0.108

Asia WGS AF: 0.0950 AC: 330 AN: 3478

EpiCase AF: 0.164

EpiControl AF: 0.166

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Sep 04, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.8
DANN	Benign	0.67
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2307418; hg19: chr1-161200586;