rs1526267

Positions:

• chr9-99827463-T-C

Variant summary

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

The NM_006981.4(NR4A3):​c.-2-578T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,024 control chromosomes in the GnomAD database, including 43,398 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 0.75 (43398 hom., cov: 31)
• Consequence: NR4A3 NM_006981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291

Genes affected

NR4A3 (HGNC:7982): (nuclear receptor subfamily 4 group A member 3) This gene encodes a member of the steroid-thyroid hormone-retinoid receptor superfamily. The encoded protein may act as a transcriptional activator. The protein can efficiently bind the NGFI-B Response Element (NBRE). Three different versions of extraskeletal myxoid chondrosarcomas (EMCs) are the result of reciprocal translocations between this gene and other genes. The translocation breakpoints are associated with Nuclear Receptor Subfamily 4, Group A, Member 3 (on chromosome 9) and either Ewing Sarcome Breakpoint Region 1 (on chromosome 22), RNA Polymerase II, TATA Box-Binding Protein-Associated Factor, 68-KD (on chromosome 17), or Transcription factor 12 (on chromosome 15). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

STX17-DT (HGNC:51174): (STX17 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR4A3	NM_006981.4	c.-2-578T>C		intron_variant		ENST00000395097.7
NR4A3	XM_017015162.2	c.-6T>C		5_prime_UTR_variant	3/9
NR4A3	NM_173199.4	c.-2-578T>C		intron_variant
NR4A3	NM_173200.3	c.32-578T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR4A3	ENST00000395097.7	c.-2-578T>C		intron_variant		1	NM_006981.4	P1
STX17-DT	ENST00000655615.1	n.268+11523A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113551 AN: 151906 Hom.: 43344 Cov.: 31

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.748 AC: 113676 AN: 152024 Hom.: 43398 Cov.: 31 AF XY: 0.738 AC XY: 54811 AN XY: 74298

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.744

Alfa AF: 0.746 Hom.: 13083

Bravo AF: 0.756

Asia WGS AF: 0.533 AC: 1856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	18
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1526267; hg19: chr9-102589745;