chr6-15516054-G-A

Variant names:

• chr6-15516054-G-A
• rs9396591
• NM_004973.4:c.3451-1107G>A

Variant summary

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

The NM_004973.4(JARID2):​c.3451-1107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 150,742 control chromosomes in the GnomAD database, including 4,857 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 0.23 (4857 hom., cov: 31)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 3 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: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004973.4. 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
	JARID2	NM_004973.4	MANE Select	c.3451-1107G>A		intron	N/A	NP_004964.2
	JARID2	NM_001267040.1		c.2935-1107G>A		intron	N/A	NP_001253969.1	Q92833-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JARID2	ENST00000341776.7	TSL:1 MANE Select	c.3451-1107G>A		intron	N/A	ENSP00000341280.2	Q92833-1
	JARID2	ENST00000853926.1		c.3451-1107G>A		intron	N/A	ENSP00000523985.1
	JARID2	ENST00000853927.1		c.3451-1107G>A		intron	N/A	ENSP00000523986.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 34951 AN: 150692 Hom.: 4857 Cov.: 31

Gnomad AFR AF: 0.0815

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.232 AC: 34949 AN: 150742 Hom.: 4857 Cov.: 31 AF XY: 0.241 AC XY: 17692 AN XY: 73518

African (AFR) AF: 0.0815 AC: 3338 AN: 40960

American (AMR) AF: 0.284 AC: 4301 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 983 AN: 3466

East Asian (EAS) AF: 0.430 AC: 2202 AN: 5118

South Asian (SAS) AF: 0.356 AC: 1704 AN: 4784

European-Finnish (FIN) AF: 0.356 AC: 3613 AN: 10158

Middle Eastern (MID) AF: 0.151 AC: 43 AN: 284

European-Non Finnish (NFE) AF: 0.265 AC: 18011 AN: 67840

Other (OTH) AF: 0.227 AC: 471 AN: 2078

Alfa AF: 0.243 Hom.: 2795

Bravo AF: 0.218

Asia WGS AF: 0.374 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.70
DANN	Benign	0.46
PhyloP100		-0.031
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: rs9396591; hg19: chr6-15516285;