rs744690

Positions:

• chr12-52047700-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001202234.2(NR4A1):​c.160+5771T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,166 control chromosomes in the GnomAD database, including 3,348 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 0.18 (3348 hom., cov: 33)
• Consequence: NR4A1 NM_001202234.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355

Genes affected

NR4A1 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR4A1	NM_001202234.2	c.160+5771T>G		intron_variant			NP_001189163.1
NR4A1	NM_001202233.2	c.37+5771T>G		intron_variant			NP_001189162.1
NR4A1	XM_047428755.1	c.745+5771T>G		intron_variant			XP_047284711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NR4A1	ENST00000478250.1	n.185+3789T>G		intron_variant		1
NR4A1	ENST00000549102.1	n.487+3789T>G		intron_variant		1
NR4A1	ENST00000545748.5	c.160+5771T>G		intron_variant		2		ENSP00000440864.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28000 AN: 152048 Hom.: 3330 Cov.: 33

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.184 AC: 28030 AN: 152166 Hom.: 3348 Cov.: 33 AF XY: 0.193 AC XY: 14341 AN XY: 74402

Gnomad4 AFR AF: 0.0955

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.269

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.198

Alfa AF: 0.171 Hom.: 750

Bravo AF: 0.202

Asia WGS AF: 0.317 AC: 1103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs744690; hg19: chr12-52441484;