rs2701129

Variant names:

• chr12-52035693-T-G
• rs2701129
• NM_001202233.2:c.-83-6117T>G

Variant summary

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

The NM_001202233.2(NR4A1):​c.-83-6117T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,070 control chromosomes in the GnomAD database, including 8,654 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 0.26 (8654 hom., cov: 32)
• Consequence: NR4A1 NM_001202233.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 13 publications found

Genes affected

NR4A1 (HGNC:7980): (nuclear receptor subfamily 4 group A member 1) This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. Expression is induced by phytohemagglutinin in human lymphocytes and by serum stimulation of arrested fibroblasts. The encoded protein acts as a nuclear transcription factor. Translocation of the protein from the nucleus to mitochondria induces apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001202233.2. 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
	NR4A1	NM_001202233.2		c.-83-6117T>G		intron	N/A	NP_001189162.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR4A1	ENST00000360284.7	TSL:2	c.-83-6117T>G		intron	N/A	ENSP00000353427.3
	NR4A1	ENST00000548977.5	TSL:2	c.-83-6117T>G		intron	N/A	ENSP00000456633.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39185 AN: 151952 Hom.: 8612 Cov.: 32

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.258 AC: 39291 AN: 152070 Hom.: 8654 Cov.: 32 AF XY: 0.253 AC XY: 18811 AN XY: 74360

African (AFR) AF: 0.606 AC: 25101 AN: 41416

American (AMR) AF: 0.147 AC: 2248 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3468

East Asian (EAS) AF: 0.105 AC: 545 AN: 5174

South Asian (SAS) AF: 0.115 AC: 556 AN: 4830

European-Finnish (FIN) AF: 0.102 AC: 1077 AN: 10598

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8646 AN: 67988

Other (OTH) AF: 0.221 AC: 466 AN: 2110

Alfa AF: 0.154 Hom.: 5671

Bravo AF: 0.273

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.84
PhyloP100		0.037
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: rs2701129; hg19: chr12-52429477;