rs201142495

Variant names:

• chr8-142664634-G-A
• rs201142495
• NM_003724.4:c.1425C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-142664634-G-A
• chr8-142664634-G-C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003724.4(JRK):​c.1425C>T​(p.Gly475Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,611,100 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00090 (2 hom., cov: 34)
  • Exomes 𝑓: 0.000090 (0 hom.)
• Consequence: JRK NM_003724.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.83
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-142664634-G-A is Benign according to our data. Variant chr8-142664634-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2068995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.83 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 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.1425C>T	p.Gly475Gly	synonymous	Exon 2 of 2	NP_003715.3	O75564-2
	JRK	NM_001077527.3		c.1425C>T	p.Gly475Gly	synonymous	Exon 2 of 3	NP_001070995.2	O75564-1
	JRK	NM_001279352.2		c.1425C>T	p.Gly475Gly	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.1425C>T	p.Gly475Gly	synonymous	Exon 2 of 2	ENSP00000482410.1	O75564-2
	JRK	ENST00000614134.1	TSL:1	c.1425C>T	p.Gly475Gly	synonymous	Exon 2 of 2	ENSP00000485390.1	O75564-2
	JRK	ENST00000571961.7	TSL:1	c.1425C>T	p.Gly475Gly	synonymous	Exon 2 of 3	ENSP00000461610.1	O75564-1

Frequencies

GnomAD3 genomes AF: 0.000796 AC: 121 AN: 152098 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.00268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000221 AC: 53 AN: 239740 AF XY: 0.000191

Gnomad AFR exome AF: 0.00325

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000905 AC: 132 AN: 1458878 Hom.: 0 Cov.: 71 AF XY: 0.0000896 AC XY: 65 AN XY: 725674

African (AFR) AF: 0.00272 AC: 91 AN: 33452

American (AMR) AF: 0.000202 AC: 9 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26036

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39678

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51940

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111328

Other (OTH) AF: 0.000348 AC: 21 AN: 60332

GnomAD4 genome AF: 0.000900 AC: 137 AN: 152222 Hom.: 2 Cov.: 34 AF XY: 0.000873 AC XY: 65 AN XY: 74438

African (AFR) AF: 0.00306 AC: 127 AN: 41546

American (AMR) AF: 0.000523 AC: 8 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000106 Hom.: 0

Bravo AF: 0.000929

ClinVar

ClinVar submissions

Significance: Likely 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	0.14
DANN	Benign	0.74
PhyloP100		-3.8

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: rs201142495; hg19: chr8-143746051;