rs6459404

Variant names:

• chr6-15281189-T-C
• rs6459404
• NM_004973.4:c.45+34605T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004973.4(JARID2):​c.45+34605T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 152,010 control chromosomes in the GnomAD database, including 19,716 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (19716 hom., cov: 31)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820
• Publications: 5 publications found

Genes affected

JARID2 (HGNC:6196): (jumonji and AT-rich interaction domain containing 2) This gene encodes a Jumonji- and AT-rich interaction domain (ARID)-domain-containing protein. The encoded protein is a DNA-binding protein that functions as a transcriptional repressor. This protein interacts with the Polycomb repressive complex 2 (PRC2) which plays an essential role in regulating gene expression during embryonic development. This protein facilitates the recruitment of the PRC2 complex to target genes. Alternate splicing results in multiple transcript variants. Mutations in this gene are associated with chronic myeloid malignancies. [provided by RefSeq, May 2012]

JARID2 Gene-Disease associations (from GenCC):

• developmental delay with variable intellectual disability and dysmorphic facies

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.45+34605T>C		intron_variant	Intron 1 of 17	ENST00000341776.7	NP_004964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JARID2	ENST00000341776.7	c.45+34605T>C		intron_variant	Intron 1 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.-472+32225T>C		intron_variant	Intron 1 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77366 AN: 151896 Hom.: 19692 Cov.: 31

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.488

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.509 AC: 77433 AN: 152010 Hom.: 19716 Cov.: 31 AF XY: 0.514 AC XY: 38185 AN XY: 74286

African (AFR) AF: 0.534 AC: 22142 AN: 41460

American (AMR) AF: 0.483 AC: 7375 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1812 AN: 3466

East Asian (EAS) AF: 0.566 AC: 2914 AN: 5146

South Asian (SAS) AF: 0.557 AC: 2686 AN: 4826

European-Finnish (FIN) AF: 0.531 AC: 5605 AN: 10548

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33195 AN: 67974

Other (OTH) AF: 0.485 AC: 1026 AN: 2114

Alfa AF: 0.491 Hom.: 30649

Bravo AF: 0.505

Asia WGS AF: 0.520 AC: 1808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.33
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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: rs6459404; hg19: chr6-15281420;