8-142664997-G-A

Position:

• chr8-142664997-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_003724.4(JRK):​c.1062C>T​(p.His354His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 720,002 control chromosomes in the GnomAD database, including 126,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (24108 hom., cov: 33)
  • Exomes 𝑓: 0.59 (102739 hom.)
• Consequence: JRK NM_003724.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0500

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 8-142664997-G-A is Benign according to our data. Variant chr8-142664997-G-A is described in ClinVar as [Benign]. Clinvar id is 769348.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JRK	NM_003724.4	c.1062C>T	p.His354His	synonymous_variant	2/2	ENST00000612905.2	NP_003715.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JRK	ENST00000612905.2	c.1062C>T	p.His354His	synonymous_variant	2/2	2	NM_003724.4	ENSP00000482410.1
JRK	ENST00000614134.1	c.1062C>T	p.His354His	synonymous_variant	2/2	1		ENSP00000485390.1
JRK	ENST00000571961.7	c.1062C>T	p.His354His	synonymous_variant	2/3	1		ENSP00000461610.1
JRK	ENST00000615982.4	c.1062C>T	p.His354His	synonymous_variant	2/4	1		ENSP00000483808.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83191 AN: 151938 Hom.: 24101 Cov.: 33

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.557

GnomAD4 exome AF: 0.594 AC: 337637 AN: 567946 Hom.: 102739 Cov.: 5 AF XY: 0.585 AC XY: 179027 AN XY: 305910

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.702

Gnomad4 ASJ exome AF: 0.523

Gnomad4 EAS exome AF: 0.496

Gnomad4 SAS exome AF: 0.455

Gnomad4 FIN exome AF: 0.682

Gnomad4 NFE exome AF: 0.628

Gnomad4 OTH exome AF: 0.565

GnomAD4 genome AF: 0.547 AC: 83211 AN: 152056 Hom.: 24108 Cov.: 33 AF XY: 0.548 AC XY: 40704 AN XY: 74310

Gnomad4 AFR AF: 0.350

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.552

Alfa AF: 0.603 Hom.: 33562

Bravo AF: 0.538

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.54

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs754957; hg19: chr8-143746416;