chr6-15281189-T-C

Position:

• chr6-15281189-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.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

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=-0.96).
• 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/exons	MANE	UniProt
JARID2	NM_004973.4	c.45+34605T>C		intron_variant		ENST00000341776.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JARID2	ENST00000341776.7	c.45+34605T>C		intron_variant		1	NM_004973.4	P2
JARID2	ENST00000397311.4	c.-472+32225T>C		intron_variant		2		A2

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

Gnomad4 AFR AF: 0.534

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.485

Alfa AF: 0.491 Hom.: 24115

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs6459404; hg19: chr6-15281420;