rs2242107

Positions:

• chr12-52043707-G-A
• chr12-52043707-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000549102.1(NR4A1):​n.283G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 1,261,206 control chromosomes in the GnomAD database, including 71,339 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 0.41 (14782 hom., cov: 33)
  • Exomes 𝑓: 0.31 (56557 hom.)
• Consequence: NR4A1 ENST00000549102.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.30

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR4A1	XM_017019248.2	c.759G>A	p.Pro253=	synonymous_variant	3/4		XP_016874737.1
NR4A1	NM_001202233.2	c.37+1778G>A		intron_variant			NP_001189162.1
NR4A1	NM_001202234.2	c.160+1778G>A		intron_variant			NP_001189163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR4A1	ENST00000549102.1	n.283G>A		non_coding_transcript_exon_variant	1/2	1
NR4A1	ENST00000360284.7	c.37+1778G>A		intron_variant		2		ENSP00000353427
NR4A1	ENST00000545748.5	c.160+1778G>A		intron_variant		2		ENSP00000440864

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62905 AN: 151964 Hom.: 14739 Cov.: 33

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.397

GnomAD4 exome AF: 0.308 AC: 341473 AN: 1109122 Hom.: 56557 Cov.: 32 AF XY: 0.310 AC XY: 168196 AN XY: 542500

Gnomad4 AFR exome AF: 0.626

Gnomad4 AMR exome AF: 0.602

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.423

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.330

GnomAD4 genome AF: 0.414 AC: 63016 AN: 152084 Hom.: 14782 Cov.: 33 AF XY: 0.419 AC XY: 31175 AN XY: 74342

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.399

Alfa AF: 0.310 Hom.: 8862

Bravo AF: 0.442

Asia WGS AF: 0.467 AC: 1623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2242107; hg19: chr12-52437491;