rs1235718133

Variant names:

• chr1-58782512-C-A
• rs1235718133
• NM_002228.4:c.559G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-58782512-C-A
• chr1-58782512-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002228.4(JUN):​c.559G>T​(p.Ala187Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,418,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: JUN NM_002228.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.47
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1879077).

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.559G>T	p.Ala187Ser	missense	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.559G>T	p.Ala187Ser	missense	Exon 1 of 1	ENSP00000360266.2	P05412
	JUN	ENST00000710273.1		c.625G>T	p.Ala209Ser	missense	Exon 1 of 1	ENSP00000518166.1	A0AA34QVR9
	JUN	ENST00000678696.1		n.559G>T		non_coding_transcript_exon	Exon 1 of 4	ENSP00000503132.1	P05412

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000113 AC: 2 AN: 177482 AF XY: 0.0000202

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000263

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1418744 Hom.: 0 Cov.: 31 AF XY: 0.00000284 AC XY: 2 AN XY: 703678

African (AFR) AF: 0.0000306 AC: 1 AN: 32648

American (AMR) AF: 0.00 AC: 0 AN: 39352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25138

East Asian (EAS) AF: 0.00 AC: 0 AN: 38554

South Asian (SAS) AF: 0.00 AC: 0 AN: 83136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5678

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1096584

Other (OTH) AF: 0.00 AC: 0 AN: 58946

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.0015
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.5
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.073
Sift	Benign	0.14	T
Sift4G	Benign	0.34	T
Polyphen		0.095	B
Vest4		0.31
MutPred		0.48		Gain of glycosylation at A187 (P = 0.0049)
MVP		0.37
MPC		0.91
ClinPred		0.26	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.13
gMVP		0.22
Mutation Taster		=74/26	polymorphism

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: rs1235718133; hg19: chr1-59248184;