rs2701124

Positions:

• chr12-52054373-G-A
• chr12-52054373-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_173157.3(NR4A1):​c.45G>A​(p.Pro15Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 1,613,194 control chromosomes in the GnomAD database, including 8,342 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 0.14 (2051 hom., cov: 32)
  • Exomes 𝑓: 0.084 (6291 hom.)
• Consequence: NR4A1 NM_173157.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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]

NR4A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=-1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR4A1	NM_173157.3	c.45G>A	p.Pro15Pro	synonymous_variant	2/7	ENST00000394825.6	NP_775180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR4A1	ENST00000394825.6	c.45G>A	p.Pro15Pro	synonymous_variant	2/7	1	NM_173157.3	ENSP00000378302.1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21044 AN: 151832 Hom.: 2041 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.0856

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.0940

Gnomad SAS AF: 0.0983

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.0949 AC: 23729 AN: 249982 Hom.: 1522 AF XY: 0.0932 AC XY: 12596 AN XY: 135148

Gnomad AFR exome AF: 0.289

Gnomad AMR exome AF: 0.0477

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.0874

Gnomad SAS exome AF: 0.108

Gnomad FIN exome AF: 0.0888

Gnomad NFE exome AF: 0.0796

Gnomad OTH exome AF: 0.0913

GnomAD4 exome AF: 0.0836 AC: 122165 AN: 1461244 Hom.: 6291 Cov.: 31 AF XY: 0.0842 AC XY: 61192 AN XY: 726916

Gnomad4 AFR exome AF: 0.292

Gnomad4 AMR exome AF: 0.0513

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.0876

Gnomad4 NFE exome AF: 0.0739

Gnomad4 OTH exome AF: 0.0961

GnomAD4 genome AF: 0.139 AC: 21086 AN: 151950 Hom.: 2051 Cov.: 32 AF XY: 0.137 AC XY: 10199 AN XY: 74284

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.0855

Gnomad4 ASJ AF: 0.0998

Gnomad4 EAS AF: 0.0944

Gnomad4 SAS AF: 0.0973

Gnomad4 FIN AF: 0.0807

Gnomad4 NFE AF: 0.0810

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0929 Hom.: 1045

Bravo AF: 0.142

Asia WGS AF: 0.128 AC: 443 AN: 3478

EpiCase AF: 0.0838

EpiControl AF: 0.0773

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	3.1
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs2701124; hg19: chr12-52448157; COSMIC: COSV54482723; COSMIC: COSV54482723;