NM_003724.4:c.1426A>G

Variant names:

• chr8-142664633-T-C
• rs2976399
• NM_003724.4:c.1426A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 19 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 -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 VariationId 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.

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.1426A>G	p.Arg476Gly	missense	Exon 2 of 2	NP_003715.3	O75564-2
	JRK	NM_001077527.3		c.1426A>G	p.Arg476Gly	missense	Exon 2 of 3	NP_001070995.2	O75564-1
	JRK	NM_001279352.2		c.1426A>G	p.Arg476Gly	missense	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.1426A>G	p.Arg476Gly	missense	Exon 2 of 2	ENSP00000482410.1	O75564-2
	JRK	ENST00000614134.1	TSL:1	c.1426A>G	p.Arg476Gly	missense	Exon 2 of 2	ENSP00000485390.1	O75564-2
	JRK	ENST00000571961.7	TSL:1	c.1426A>G	p.Arg476Gly	missense	Exon 2 of 3	ENSP00000461610.1	O75564-1

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

African (AFR) AF: 0.554 AC: 18518 AN: 33450

American (AMR) AF: 0.742 AC: 32992 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 14559 AN: 26032

East Asian (EAS) AF: 0.537 AC: 21287 AN: 39632

South Asian (SAS) AF: 0.482 AC: 41326 AN: 85794

European-Finnish (FIN) AF: 0.730 AC: 37855 AN: 51872

Middle Eastern (MID) AF: 0.510 AC: 2938 AN: 5764

European-Non Finnish (NFE) AF: 0.685 AC: 761350 AN: 1111062

Other (OTH) AF: 0.632 AC: 38129 AN: 60316

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

African (AFR) AF: 0.565 AC: 23440 AN: 41494

American (AMR) AF: 0.711 AC: 10872 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1940 AN: 3470

East Asian (EAS) AF: 0.530 AC: 2731 AN: 5152

South Asian (SAS) AF: 0.475 AC: 2295 AN: 4832

European-Finnish (FIN) AF: 0.739 AC: 7834 AN: 10598

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46582 AN: 67972

Other (OTH) AF: 0.629 AC: 1330 AN: 2114

Alfa AF: 0.648 Hom.: 28850

Bravo AF: 0.639

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
AlphaMissense	Benign	0.058
CADD	Benign	1.5
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0065	T
PhyloP100		-0.073
Sift4G	Benign	0.32	T
Vest4		0.038
gMVP		0.18

Splicing

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

Other links and lift over

dbSNP: rs2976399;