chr8-142664652-C-T

Variant names:

• chr8-142664652-C-T
• rs3735999
• NM_003724.4:c.1407G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_003724.4(JRK):​c.1407G>A​(p.Pro469Pro) 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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003724.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JRK	NM_003724.4	MANE Select	c.1407G>A	p.Pro469Pro	synonymous	Exon 2 of 2	NP_003715.3	O75564-2
	JRK	NM_001077527.3		c.1407G>A	p.Pro469Pro	synonymous	Exon 2 of 3	NP_001070995.2	O75564-1
	JRK	NM_001279352.2		c.1407G>A	p.Pro469Pro	synonymous	Exon 2 of 4	NP_001266281.1	O75564-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JRK	ENST00000612905.2	TSL:2 MANE Select	c.1407G>A	p.Pro469Pro	synonymous	Exon 2 of 2	ENSP00000482410.1	O75564-2
	JRK	ENST00000614134.1	TSL:1	c.1407G>A	p.Pro469Pro	synonymous	Exon 2 of 2	ENSP00000485390.1	O75564-2
	JRK	ENST00000571961.7	TSL:1	c.1407G>A	p.Pro469Pro	synonymous	Exon 2 of 3	ENSP00000461610.1	O75564-1

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

African (AFR) AF: 0.338 AC: 11302 AN: 33430

American (AMR) AF: 0.710 AC: 31567 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 13569 AN: 26012

East Asian (EAS) AF: 0.497 AC: 19686 AN: 39628

South Asian (SAS) AF: 0.451 AC: 38648 AN: 85728

European-Finnish (FIN) AF: 0.683 AC: 35781 AN: 52408

Middle Eastern (MID) AF: 0.477 AC: 2751 AN: 5764

European-Non Finnish (NFE) AF: 0.631 AC: 701488 AN: 1110844

Other (OTH) AF: 0.573 AC: 34553 AN: 60300

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

African (AFR) AF: 0.353 AC: 14661 AN: 41480

American (AMR) AF: 0.662 AC: 10133 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1803 AN: 3472

East Asian (EAS) AF: 0.497 AC: 2552 AN: 5134

South Asian (SAS) AF: 0.442 AC: 2134 AN: 4826

European-Finnish (FIN) AF: 0.692 AC: 7326 AN: 10588

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42946 AN: 67966

Other (OTH) AF: 0.554 AC: 1170 AN: 2112

Alfa AF: 0.601 Hom.: 40936

Bravo AF: 0.540

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
PhyloP100		-0.42

Splicing

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

Other links and lift over

dbSNP: rs3735999; hg19: chr8-143746069;