Variant 8-142665573-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003724.4(JRK):c.486G>C(p.Ala162=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00792 in 718,526 control chromosomes in the GnomAD database, including 348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A162A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0086 ( 51 hom., cov: 34)

Exomes 𝑓: 0.0077 ( 297 hom. )

Consequence

JRK
NM_003724.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.03

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 made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

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

BP6

Variant 8-142665573-C-G is Benign according to our data. Variant chr8-142665573-C-G is described in ClinVar as [Benign]. Clinvar id is 769748.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JRK	NM_003724.4 linkuse as main transcript	c.486G>C	p.Ala162=	synonymous_variant	2/2	ENST00000612905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JRK	ENST00000612905.2 linkuse as main transcript	c.486G>C	p.Ala162=	synonymous_variant	2/2	2	NM_003724.4	P2	O75564-2
JRK	ENST00000614134.1 linkuse as main transcript	c.486G>C	p.Ala162=	synonymous_variant	2/2	1		P2	O75564-2
JRK	ENST00000571961.7 linkuse as main transcript	c.486G>C	p.Ala162=	synonymous_variant	2/3	1		A2	O75564-1
JRK	ENST00000615982.4 linkuse as main transcript	c.486G>C	p.Ala162=	synonymous_variant	2/4	1		A2	O75564-1

Frequencies

GnomAD3 genomes

AF:

0.00856

AC:

1303

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00282

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0739

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0207

AC:

3142

AN:

151968

Hom.:

233

AF XY:

0.0158

AC XY:

1275

AN XY:

80626

show subpopulations

Gnomad AFR exome

AF:

0.00251

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000790

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000313

Gnomad OTH exome

AF:

0.0183

GnomAD4 exome

AF:

0.00774

AC:

4382

AN:

566174

Hom.:

297

Cov.:

AF XY:

0.00609

AC XY:

1861

AN XY:

305434

show subpopulations

Gnomad4 AFR exome

AF:

0.00272

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000125

Gnomad4 SAS exome

AF:

0.000717

Gnomad4 FIN exome

AF:

0.0000205

Gnomad4 NFE exome

AF:

0.000233

Gnomad4 OTH exome

AF:

0.00694

GnomAD4 genome

AF:

0.00857

AC:

1306

AN:

152352

Hom.:

Cov.:

AF XY:

0.00946

AC XY:

705

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00281

Gnomad4 AMR

AF:

0.0740

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.0149

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.049

DANN

Benign

0.76

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over