rs9654600

Positions:

• chr6-15513882-T-A
• chr6-15513882-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004973.4(JARID2):​c.3450+460T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,316 control chromosomes in the GnomAD database, including 1,234 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 0.12 (1234 hom., cov: 34)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JARID2	NM_004973.4	c.3450+460T>A		intron_variant		ENST00000341776.7	NP_004964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JARID2	ENST00000341776.7	c.3450+460T>A		intron_variant		1	NM_004973.4	ENSP00000341280	P2
JARID2	ENST00000397311.4	c.2934+460T>A		intron_variant		2		ENSP00000380478	A2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17539 AN: 152198 Hom.: 1237 Cov.: 34

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.115 AC: 17556 AN: 152316 Hom.: 1234 Cov.: 34 AF XY: 0.115 AC XY: 8561 AN XY: 74478

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0688

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0589

Gnomad4 NFE AF: 0.0748

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0157 Hom.: 5

Bravo AF: 0.125

Asia WGS AF: 0.172 AC: 598 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.1
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9654600; hg19: chr6-15514113;