rs11688

chr1-58782321-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002228.4(JUN):c.750G>A(p.Gln250=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0577 in 1,614,190 control chromosomes in the GnomAD database, including 3,798 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 0.093 (1064 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2734 hom.)
• Consequence: JUN NM_002228.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

Genes affected

JUN (HGNC:6204): (Jun proto-oncogene, AP-1 transcription factor subunit) This gene is the putative transforming gene of avian sarcoma virus 17. It encodes a protein which is highly similar to the viral protein, and which interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=1.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JUN	NM_002228.4	c.750G>A	p.Gln250=	synonymous_variant	1/1	ENST00000371222.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JUN	ENST00000371222.4	c.750G>A	p.Gln250=	synonymous_variant	1/1		NM_002228.4	P1
JUN	ENST00000710273.1	c.816G>A	p.Gln272=	synonymous_variant	1/1
JUN	ENST00000678696.1	c.750G>A	p.Gln250=	synonymous_variant, NMD_transcript_variant	1/4

Frequencies

GnomAD3 genomes AF: 0.0930 AC: 14146 AN: 152186 Hom.: 1062 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0578

Gnomad ASJ AF: 0.0136

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.0499

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.0788

GnomAD3 exomes AF: 0.0528 AC: 13268 AN: 251158 Hom.: 630 AF XY: 0.0495 AC XY: 6723 AN XY: 135862

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.0324

Gnomad ASJ exome AF: 0.0183

Gnomad EAS exome AF: 0.0284

Gnomad SAS exome AF: 0.0183

Gnomad FIN exome AF: 0.0471

Gnomad NFE exome AF: 0.0537

Gnomad OTH exome AF: 0.0518

GnomAD4 exome AF: 0.0540 AC: 78897 AN: 1461886 Hom.: 2734 Cov.: 31 AF XY: 0.0523 AC XY: 38040 AN XY: 727246

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.0345

Gnomad4 ASJ exome AF: 0.0176

Gnomad4 EAS exome AF: 0.0221

Gnomad4 SAS exome AF: 0.0185

Gnomad4 FIN exome AF: 0.0483

Gnomad4 NFE exome AF: 0.0550

Gnomad4 OTH exome AF: 0.0539

GnomAD4 genome AF: 0.0931 AC: 14172 AN: 152304 Hom.: 1064 Cov.: 32 AF XY: 0.0907 AC XY: 6755 AN XY: 74472

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.0578

Gnomad4 ASJ AF: 0.0136

Gnomad4 EAS AF: 0.0208

Gnomad4 SAS AF: 0.0159

Gnomad4 FIN AF: 0.0499

Gnomad4 NFE AF: 0.0538

Gnomad4 OTH AF: 0.0780

Alfa AF: 0.0582 Hom.: 553

Bravo AF: 0.0981

Asia WGS AF: 0.0360 AC: 126 AN: 3478

EpiCase AF: 0.0485

EpiControl AF: 0.0483

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	9.1
Dann	Benign	0.97

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

Publications

LitVar

Other links and lift over

dbSNP: rs11688; hg19: chr1-59247993; COSMIC: COSV64664225; COSMIC: COSV64664225;