rs11688

Variant names:

• chr1-58782321-C-T
• rs11688
• NM_002228.4:c.750G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002228.4(JUN):​c.750G>A​(p.Gln250Gln) 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
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002228.4. 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
	JUN	NM_002228.4	MANE Select	c.750G>A	p.Gln250Gln	synonymous	Exon 1 of 1	NP_002219.1	P05412

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JUN	ENST00000371222.4	TSL:6 MANE Select	c.750G>A	p.Gln250Gln	synonymous	Exon 1 of 1	ENSP00000360266.2	P05412
	JUN	ENST00000710273.1		c.816G>A	p.Gln272Gln	synonymous	Exon 1 of 1	ENSP00000518166.1	A0AA34QVR9
	JUN	ENST00000678696.1		n.750G>A		non_coding_transcript_exon	Exon 1 of 4	ENSP00000503132.1	P05412

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

GnomAD2 exomes AF: 0.0528 AC: 13268 AN: 251158 AF XY: 0.0495

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 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

African (AFR) AF: 0.216 AC: 7241 AN: 33478

American (AMR) AF: 0.0345 AC: 1544 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 460 AN: 26136

East Asian (EAS) AF: 0.0221 AC: 877 AN: 39700

South Asian (SAS) AF: 0.0185 AC: 1600 AN: 86258

European-Finnish (FIN) AF: 0.0483 AC: 2578 AN: 53420

Middle Eastern (MID) AF: 0.0335 AC: 193 AN: 5766

European-Non Finnish (NFE) AF: 0.0550 AC: 61150 AN: 1112008

Other (OTH) AF: 0.0539 AC: 3254 AN: 60396

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

African (AFR) AF: 0.208 AC: 8645 AN: 41550

American (AMR) AF: 0.0578 AC: 884 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 47 AN: 3468

East Asian (EAS) AF: 0.0208 AC: 108 AN: 5184

South Asian (SAS) AF: 0.0159 AC: 77 AN: 4832

European-Finnish (FIN) AF: 0.0499 AC: 530 AN: 10614

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0538 AC: 3661 AN: 68032

Other (OTH) AF: 0.0780 AC: 165 AN: 2116

Alfa AF: 0.0612 Hom.: 778

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.1
DANN	Benign	0.97
PhyloP100		1.7
Mutation Taster		=97/3	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: rs11688; hg19: chr1-59247993; COSMIC: COSV64664225; COSMIC: COSV64664225;