Variant 8-142664551-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003724.4(JRK):c.1508G>A(p.Arg503Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00778 in 1,607,948 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0080 ( 64 hom. )

Consequence

JRK
NM_003724.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.80

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037443936).

BP6

Variant 8-142664551-C-T is Benign according to our data. Variant chr8-142664551-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 779431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JRK	NM_003724.4 link	c.1508G>A	p.Arg503Gln	missense_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 link	c.1508G>A	p.Arg503Gln	missense_variant	2/2	2	NM_003724.4	ENSP00000482410.1	O75564-2
JRK	ENST00000614134.1 link	c.1508G>A	p.Arg503Gln	missense_variant	2/2	1		ENSP00000485390.1	O75564-2
JRK	ENST00000571961.7 link	c.1508G>A	p.Arg503Gln	missense_variant	2/3	1		ENSP00000461610.1	O75564-1
JRK	ENST00000615982.4 link	c.1508G>A	p.Arg503Gln	missense_variant	2/4	1		ENSP00000483808.1	O75564-1

Frequencies

GnomAD3 genomes

AF:

0.00532

AC:

810

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00841

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00573

AC:

1329

AN:

231884

Hom.:

AF XY:

0.00575

AC XY:

733

AN XY:

127400

show subpopulations

Gnomad AFR exome

AF:

0.00157

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.00930

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00804

AC:

11701

AN:

1455636

Hom.:

Cov.:

AF XY:

0.00775

AC XY:

5611

AN XY:

723892

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00109

Gnomad4 ASJ exome

AF:

0.00100

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.0139

Gnomad4 NFE exome

AF:

0.00947

Gnomad4 OTH exome

AF:

0.00599

GnomAD4 genome

AF:

0.00532

AC:

810

AN:

152312

Hom.:

Cov.:

AF XY:

0.00473

AC XY:

352

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0120

Gnomad4 NFE

AF:

0.00841

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00781

Hom.:

Bravo

AF:

0.00457

TwinsUK

AF:

0.00836

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.000939

AC:

ESP6500EA

AF:

0.00860

AC:

ExAC

AF:

0.00595

AC:

718

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	JRK: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.10

DANN

Benign

0.83

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.59

.;T;.;T

MetaRNN

Benign

0.0037

T;T;T;T

PrimateAI

Benign

0.41

Sift4G

Benign

0.91

T;T;T;T

Vest4

0.021

MVP

0.32

GERP RS

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.029

gMVP

0.089

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