chr8-142664532-C-T

Variant names:

• chr8-142664532-C-T
• rs147803227
• NM_003724.4:c.1527G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_003724.4(JRK):​c.1527G>A​(p.Ala509Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00463 in 1,608,302 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (27 hom.)
• Consequence: JRK NM_003724.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.75
• Publications: 2 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-142664532-C-T is Benign according to our data. Variant chr8-142664532-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 715014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.75 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 gene

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.1527G>A	p.Ala509Ala	synonymous	Exon 2 of 2	NP_003715.3	O75564-2
	JRK	NM_001077527.3		c.1527G>A	p.Ala509Ala	synonymous	Exon 2 of 3	NP_001070995.2	O75564-1
	JRK	NM_001279352.2		c.1527G>A	p.Ala509Ala	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.1527G>A	p.Ala509Ala	synonymous	Exon 2 of 2	ENSP00000482410.1	O75564-2
	JRK	ENST00000614134.1	TSL:1	c.1527G>A	p.Ala509Ala	synonymous	Exon 2 of 2	ENSP00000485390.1	O75564-2
	JRK	ENST00000571961.7	TSL:1	c.1527G>A	p.Ala509Ala	synonymous	Exon 2 of 3	ENSP00000461610.1	O75564-1

Frequencies

GnomAD3 genomes AF: 0.00406 AC: 618 AN: 152218 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00351

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00542

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00419 AC: 969 AN: 231416 AF XY: 0.00431

Gnomad AFR exome AF: 0.000900

Gnomad AMR exome AF: 0.00322

Gnomad ASJ exome AF: 0.0152

Gnomad EAS exome AF: 0.0000580

Gnomad FIN exome AF: 0.000153

Gnomad NFE exome AF: 0.00528

Gnomad OTH exome AF: 0.00508

GnomAD4 exome AF: 0.00469 AC: 6827 AN: 1455966 Hom.: 27 Cov.: 35 AF XY: 0.00475 AC XY: 3437 AN XY: 724052

African (AFR) AF: 0.00129 AC: 43 AN: 33356

American (AMR) AF: 0.00403 AC: 178 AN: 44192

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 389 AN: 25954

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39486

South Asian (SAS) AF: 0.00513 AC: 439 AN: 85500

European-Finnish (FIN) AF: 0.000233 AC: 12 AN: 51408

Middle Eastern (MID) AF: 0.00608 AC: 35 AN: 5754

European-Non Finnish (NFE) AF: 0.00484 AC: 5378 AN: 1110190

Other (OTH) AF: 0.00585 AC: 352 AN: 60126

GnomAD4 genome AF: 0.00406 AC: 618 AN: 152336 Hom.: 3 Cov.: 33 AF XY: 0.00383 AC XY: 285 AN XY: 74490

African (AFR) AF: 0.000986 AC: 41 AN: 41584

American (AMR) AF: 0.00732 AC: 112 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00372 AC: 18 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00541 AC: 368 AN: 68030

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00499 Hom.: 8

Bravo AF: 0.00459

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.86
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs147803227; hg19: chr8-143745949;