chr8-142664652-C-T

Position:

• chr8-142664652-C-T

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.1407G>A​(p.Pro469=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 1,610,650 control chromosomes in the GnomAD database, including 299,496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.55 (24181 hom., cov: 33)
  • Exomes 𝑓: 0.61 (275315 hom.)
• Consequence: JRK NM_003724.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.419

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=-0.88).
• BP6: Variant 8-142664652-C-T is Benign according to our data. Variant chr8-142664652-C-T is described in ClinVar as [Benign]. Clinvar id is 769347.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.419 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JRK	NM_003724.4	c.1407G>A	p.Pro469=	synonymous_variant	2/2	ENST00000612905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JRK	ENST00000612905.2	c.1407G>A	p.Pro469=	synonymous_variant	2/2	2	NM_003724.4	P2
JRK	ENST00000614134.1	c.1407G>A	p.Pro469=	synonymous_variant	2/2	1		P2
JRK	ENST00000571961.7	c.1407G>A	p.Pro469=	synonymous_variant	2/3	1		A2
JRK	ENST00000615982.4	c.1407G>A	p.Pro469=	synonymous_variant	2/4	1		A2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83348 AN: 151962 Hom.: 24171 Cov.: 33

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.558

GnomAD4 exome AF: 0.610 AC: 889345 AN: 1458570 Hom.: 275315 Cov.: 74 AF XY: 0.604 AC XY: 438195 AN XY: 725386

Gnomad4 AFR exome AF: 0.338

Gnomad4 AMR exome AF: 0.710

Gnomad4 ASJ exome AF: 0.522

Gnomad4 EAS exome AF: 0.497

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.683

Gnomad4 NFE exome AF: 0.631

Gnomad4 OTH exome AF: 0.573

GnomAD4 genome AF: 0.548 AC: 83388 AN: 152080 Hom.: 24181 Cov.: 33 AF XY: 0.549 AC XY: 40798 AN XY: 74342

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.554

Alfa AF: 0.604 Hom.: 27325

Bravo AF: 0.540

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	-0.88
CADD	Benign	1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3735999; hg19: chr8-143746069;