6-15516478-T-C

Position:

• chr6-15516478-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.3451-683T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 152,226 control chromosomes in the GnomAD database, including 51,841 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 0.82 (51841 hom., cov: 33)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.80

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JARID2	NM_004973.4	c.3451-683T>C		intron_variant		ENST00000341776.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JARID2	ENST00000341776.7	c.3451-683T>C		intron_variant		1	NM_004973.4	P2
JARID2	ENST00000397311.4	c.2935-683T>C		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125316 AN: 152108 Hom.: 51808 Cov.: 33

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.824 AC: 125404 AN: 152226 Hom.: 51841 Cov.: 33 AF XY: 0.826 AC XY: 61489 AN XY: 74428

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.880

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.828

Alfa AF: 0.838 Hom.: 17954

Bravo AF: 0.817

Asia WGS AF: 0.841 AC: 2924 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.40

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: rs1474587; hg19: chr6-15516709;