Variant 8-142664532-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003724.4(JRK):c.1527G>A(p.Ala509Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00463 in 1,608,302 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 27 hom. )

Consequence

JRK
NM_003724.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.75

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 8-142664532-C-T is Benign according to our data. Variant chr8-142664532-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 715014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.75 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JRK	NM_003724.4 linkuse as main transcript	c.1527G>A	p.Ala509Ala	synonymous_variant	2/2	ENST00000612905.2	NP_003715.3	O75564-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
JRK	ENST00000612905.2 linkuse as main transcript	c.1527G>A	p.Ala509Ala	synonymous_variant	2/2	2	NM_003724.4	ENSP00000482410.1	O75564-2
JRK	ENST00000614134.1 linkuse as main transcript	c.1527G>A	p.Ala509Ala	synonymous_variant	2/2	1		ENSP00000485390.1	O75564-2
JRK	ENST00000571961.7 linkuse as main transcript	c.1527G>A	p.Ala509Ala	synonymous_variant	2/3	1		ENSP00000461610.1	O75564-1
JRK	ENST00000615982.4 linkuse as main transcript	c.1527G>A	p.Ala509Ala	synonymous_variant	2/4	1		ENSP00000483808.1	O75564-1

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

618

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00733

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00351

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00542

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00419

AC:

969

AN:

231416

Hom.:

AF XY:

0.00431

AC XY:

549

AN XY:

127340

show subpopulations

Gnomad AFR exome

AF:

0.000900

Gnomad AMR exome

AF:

0.00322

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.0000580

Gnomad SAS exome

AF:

0.00427

Gnomad FIN exome

AF:

0.000153

Gnomad NFE exome

AF:

0.00528

Gnomad OTH exome

AF:

0.00508

GnomAD4 exome

AF:

0.00469

AC:

6827

AN:

1455966

Hom.:

Cov.:

AF XY:

0.00475

AC XY:

3437

AN XY:

724052

show subpopulations

Gnomad4 AFR exome

AF:

0.00129

Gnomad4 AMR exome

AF:

0.00403

Gnomad4 ASJ exome

AF:

0.0150

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00513

Gnomad4 FIN exome

AF:

0.000233

Gnomad4 NFE exome

AF:

0.00484

Gnomad4 OTH exome

AF:

0.00585

GnomAD4 genome

AF:

0.00406

AC:

618

AN:

152336

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

285

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000986

Gnomad4 AMR

AF:

0.00732

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00372

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00541

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00565

Hom.:

Bravo

AF:

0.00459

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	JRK: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.9

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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