Genetic Variant NM_002228.4:c.-826C>T (chr1-58783896-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002228.4(JUN):c.-826C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 248,256 control chromosomes in the GnomAD database, including 8 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 0.00090 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0046 ( 6 hom. )

Consequence

JUN
NM_002228.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.72

Publications

4 publications found

Variant links:

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]

JUN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0009 (137/152290) while in subpopulation EAS AF = 0.021 (109/5180). AF 95% confidence interval is 0.0178. There are 2 homozygotes in GnomAd4. There are 78 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 137 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JUN	NM_002228.4 link	c.-826C>T		5_prime_UTR_variant	Exon 1 of 1	ENST00000371222.4	NP_002219.1	P05412

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
JUN	ENST00000371222.4 link	c.-826C>T	5_prime_UTR_variant	Exon 1 of 1	6	NM_002228.4	ENSP00000360266.2	P05412
JUN	ENST00000678696.1 link	n.-826C>T	non_coding_transcript_exon_variant	Exon 1 of 4			ENSP00000503132.1	P05412
JUN	ENST00000710273.1 link	c.-760C>T	5_prime_UTR_variant	Exon 1 of 1			ENSP00000518166.1
JUN	ENST00000678696.1 link	n.-826C>T	5_prime_UTR_variant	Exon 1 of 4			ENSP00000503132.1	P05412

Frequencies

GnomAD3 genomes

AF:

0.000907

AC:

138

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.0212

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00457

AC:

439

AN:

95966

Hom.:

Cov.:

AF XY:

0.00446

AC XY:

198

AN XY:

44364

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

3898

American (AMR)

AF:

0.00

AC:

AN:

2502

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

5126

East Asian (EAS)

AF:

0.0346

AC:

395

AN:

11410

South Asian (SAS)

AF:

0.00

AC:

AN:

706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14748

Middle Eastern (MID)

AF:

0.00

AC:

AN:

494

European-Non Finnish (NFE)

AF:

0.0000996

AC:

AN:

50222

Other (OTH)

AF:

0.00117

AC:

AN:

6860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

114

143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000900

AC:

137

AN:

152290

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41554

American (AMR)

AF:

0.000131

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3468

East Asian (EAS)

AF:

0.0210

AC:

109

AN:

5180

South Asian (SAS)

AF:

0.000829

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000287

Hom.:

Bravo

AF:

0.00122

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

2.7

PromoterAI

0.0020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over