12-52054373-G-A

Variant names:

• chr12-52054373-G-A
• rs2701124
• NM_173157.3:c.45G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173157.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR4A1	NM_173157.3	MANE Select	c.45G>A	p.Pro15Pro	synonymous	Exon 2 of 7	NP_775180.1	P22736-1
	NR4A1	NM_001202234.2		c.207G>A	p.Pro69Pro	synonymous	Exon 3 of 8	NP_001189163.1	F5GXF0
	NR4A1	NM_001202233.2		c.84G>A	p.Pro28Pro	synonymous	Exon 3 of 8	NP_001189162.1	P22736-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR4A1	ENST00000394825.6	TSL:1 MANE Select	c.45G>A	p.Pro15Pro	synonymous	Exon 2 of 7	ENSP00000378302.1	P22736-1
	NR4A1	ENST00000243050.5	TSL:1	c.45G>A	p.Pro15Pro	synonymous	Exon 3 of 8	ENSP00000243050.1	P22736-1
	NR4A1	ENST00000478250.1	TSL:1	n.232G>A		non_coding_transcript_exon	Exon 2 of 2

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

GnomAD2 exomes AF: 0.0949 AC: 23729 AN: 249982 AF XY: 0.0932

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 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

African (AFR) AF: 0.292 AC: 9763 AN: 33466

American (AMR) AF: 0.0513 AC: 2293 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2677 AN: 26084

East Asian (EAS) AF: 0.120 AC: 4774 AN: 39694

South Asian (SAS) AF: 0.109 AC: 9365 AN: 86200

European-Finnish (FIN) AF: 0.0876 AC: 4663 AN: 53238

Middle Eastern (MID) AF: 0.111 AC: 640 AN: 5764

European-Non Finnish (NFE) AF: 0.0739 AC: 82186 AN: 1111732

Other (OTH) AF: 0.0961 AC: 5804 AN: 60368

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

African (AFR) AF: 0.282 AC: 11669 AN: 41390

American (AMR) AF: 0.0855 AC: 1307 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0998 AC: 346 AN: 3468

East Asian (EAS) AF: 0.0944 AC: 486 AN: 5146

South Asian (SAS) AF: 0.0973 AC: 467 AN: 4800

European-Finnish (FIN) AF: 0.0807 AC: 856 AN: 10602

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.0810 AC: 5502 AN: 67954

Other (OTH) AF: 0.118 AC: 249 AN: 2106

Alfa AF: 0.0982 Hom.: 1640

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	3.1
DANN	Benign	0.76
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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