8-142664633-T-C

Position:

• chr8-142664633-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003724.4(JRK):​c.1426A>G​(p.Arg476Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,610,504 control chromosomes in the GnomAD database, including 357,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (31846 hom., cov: 33)
  • Exomes 𝑓: 0.66 (325407 hom.)
• Consequence: JRK NM_003724.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0730

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006519735).
• BP6: Variant 8-142664633-T-C is Benign according to our data. Variant chr8-142664633-T-C is described in ClinVar as [Benign]. Clinvar id is 769346.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JRK	NM_003724.4	c.1426A>G	p.Arg476Gly	missense_variant	2/2	ENST00000612905.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JRK	ENST00000612905.2	c.1426A>G	p.Arg476Gly	missense_variant	2/2	2	NM_003724.4	P2
JRK	ENST00000614134.1	c.1426A>G	p.Arg476Gly	missense_variant	2/2	1		P2
JRK	ENST00000571961.7	c.1426A>G	p.Arg476Gly	missense_variant	2/3	1		A2
JRK	ENST00000615982.4	c.1426A>G	p.Arg476Gly	missense_variant	2/4	1		A2

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97674 AN: 152010 Hom.: 31824 Cov.: 33

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.632

GnomAD4 exome AF: 0.664 AC: 968954 AN: 1458376 Hom.: 325407 Cov.: 65 AF XY: 0.658 AC XY: 477128 AN XY: 725388

Gnomad4 AFR exome AF: 0.554

Gnomad4 AMR exome AF: 0.742

Gnomad4 ASJ exome AF: 0.559

Gnomad4 EAS exome AF: 0.537

Gnomad4 SAS exome AF: 0.482

Gnomad4 FIN exome AF: 0.730

Gnomad4 NFE exome AF: 0.685

Gnomad4 OTH exome AF: 0.632

GnomAD4 genome AF: 0.643 AC: 97744 AN: 152128 Hom.: 31846 Cov.: 33 AF XY: 0.641 AC XY: 47653 AN XY: 74372

Gnomad4 AFR AF: 0.565

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.629

Alfa AF: 0.653 Hom.: 19469

Bravo AF: 0.639

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
AlphaMissense	Benign	0.058
CADD	Benign	1.5
LIST_S2	Benign	0.22	.;T;.;T
MetaRNN	Benign	0.0065	T;T;T;T
Sift4G	Benign	0.32	T;T;T;T
Vest4		0.038
gMVP		0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2976399; hg19: -;