chr12-52059498-T-C

Variant names:

• chr12-52059498-T-C
• rs2603751
• ENST00000550557.1:n.4832T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000550557.1(NR4A1):​n.4832T>C 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 0.24 in 152,116 control chromosomes in the GnomAD database, including 7,060 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 0.24 (7059 hom., cov: 33)
  • Exomes 𝑓: 0.071 (1 hom.)
• Consequence: NR4A1 ENST00000550557.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 23 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]

NR4A1AS (HGNC:54409): (NR4A1 antisense RNA)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR4A1	NM_173157.3	c.*554T>C		3_prime_UTR_variant	Exon 7 of 7	ENST00000394825.6	NP_775180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR4A1	ENST00000394825.6	c.*554T>C		3_prime_UTR_variant	Exon 7 of 7	1	NM_173157.3	ENSP00000378302.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36443 AN: 151956 Hom.: 7042 Cov.: 33

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.0714 AC: 3 AN: 42 Hom.: 1 Cov.: 0 AF XY: 0.111 AC XY: 2 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0789 AC: 3 AN: 38

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.240 AC: 36504 AN: 152074 Hom.: 7059 Cov.: 33 AF XY: 0.237 AC XY: 17617 AN XY: 74336

African (AFR) AF: 0.543 AC: 22506 AN: 41430

American (AMR) AF: 0.133 AC: 2037 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 557 AN: 3470

East Asian (EAS) AF: 0.103 AC: 536 AN: 5180

South Asian (SAS) AF: 0.170 AC: 818 AN: 4814

European-Finnish (FIN) AF: 0.120 AC: 1272 AN: 10600

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8114 AN: 67996

Other (OTH) AF: 0.200 AC: 422 AN: 2114

Alfa AF: 0.149 Hom.: 4548

Bravo AF: 0.250

Asia WGS AF: 0.189 AC: 659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.82
PhyloP100		0.27
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: rs2603751; hg19: chr12-52453282;