Genetic Variant NM_003724.4:c.1425C>G (chr8-142664634-G-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_003724.4(JRK):c.1425C>G(p.Gly475Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000186 in 1,611,100 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G475G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

JRK
NM_003724.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.83

Publications

1 publications found

Variant links:

Genes affected

JRK (HGNC:6199): (Jrk helix-turn-helix protein) This gene encodes a conserved protein that is similar to DNA-binding proteins, such as major centromere autoantigen B (CENPB). Inactivation of the related gene in mice resulted in epileptic seizures. Childhood Absence Epilepsy (CAE) has been mapped to the same chromosomal location (8q24.3) as this gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

JRK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP7

Synonymous conserved (PhyloP=-3.83 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003724.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JRK	NM_003724.4	MANE Select	c.1425C>G	p.Gly475Gly	synonymous	Exon 2 of 2	NP_003715.3	O75564-2
JRK	NM_001077527.3		c.1425C>G	p.Gly475Gly	synonymous	Exon 2 of 3	NP_001070995.2	O75564-1
JRK	NM_001279352.2		c.1425C>G	p.Gly475Gly	synonymous	Exon 2 of 4	NP_001266281.1	O75564-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JRK	ENST00000612905.2	TSL:2 MANE Select	c.1425C>G	p.Gly475Gly	synonymous	Exon 2 of 2	ENSP00000482410.1	O75564-2
JRK	ENST00000614134.1	TSL:1	c.1425C>G	p.Gly475Gly	synonymous	Exon 2 of 2	ENSP00000485390.1	O75564-2
JRK	ENST00000571961.7	TSL:1	c.1425C>G	p.Gly475Gly	synonymous	Exon 2 of 3	ENSP00000461610.1	O75564-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00291

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000259

AC:

AN:

239740

AF XY:

0.000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00349

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000194

AC:

283

AN:

1458878

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

123

AN XY:

725676

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00686

AC:

272

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

85780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51942

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111328

Other (OTH)

AF:

0.000182

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000112

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41546

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00291

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67996

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

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:

0.00

Hom.:

Bravo

AF:

0.000147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.12

(source)

DANN

Benign

0.52

PhyloP100

-3.8

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over