rs2701129

Positions:

• chr12-52035693-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR4A1	NM_001202233.2	c.-83-6117T>G		intron_variant			NP_001189162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR4A1	ENST00000360284.7	c.-83-6117T>G		intron_variant		2		ENSP00000353427.3
NR4A1	ENST00000548977.5	c.-83-6117T>G		intron_variant		2		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

Gnomad4 AFR AF: 0.606

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.221

Alfa AF: 0.143 Hom.: 3140

Bravo AF: 0.273

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2701129; hg19: chr12-52429477;