12-52054373-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_173157.3(NR4A1):​c.45G>C​(p.Pro15Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=-1.09 with no splicing effect.

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>C	p.Pro15Pro	synonymous	Exon 2 of 7	NP_775180.1	P22736-1
	NR4A1	NM_001202234.2		c.207G>C	p.Pro69Pro	synonymous	Exon 3 of 8	NP_001189163.1	F5GXF0
	NR4A1	NM_001202233.2		c.84G>C	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>C	p.Pro15Pro	synonymous	Exon 2 of 7	ENSP00000378302.1	P22736-1
	NR4A1	ENST00000243050.5	TSL:1	c.45G>C	p.Pro15Pro	synonymous	Exon 3 of 8	ENSP00000243050.1	P22736-1
	NR4A1	ENST00000478250.1	TSL:1	n.232G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1640

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	1.2
DANN	Benign	0.70
PhyloP100		-1.1

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;