NM_004973.4:c.45+28490A>G

Variant names:

• chr6-15275074-A-G
• rs6921502
• NM_004973.4:c.45+28490A>G

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+28490A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 152,016 control chromosomes in the GnomAD database, including 22,455 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 0.54 (22455 hom., cov: 31)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• 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: 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JARID2	NM_004973.4	MANE Select	c.45+28490A>G		intron	N/A	NP_004964.2
	JARID2	NM_001267040.1		c.-472+26110A>G		intron	N/A	NP_001253969.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JARID2	ENST00000341776.7	TSL:1 MANE Select	c.45+28490A>G		intron	N/A	ENSP00000341280.2
	JARID2	ENST00000397311.4	TSL:2	c.-472+26110A>G		intron	N/A	ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82031 AN: 151898 Hom.: 22417 Cov.: 31

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.540 AC: 82116 AN: 152016 Hom.: 22455 Cov.: 31 AF XY: 0.544 AC XY: 40410 AN XY: 74304

African (AFR) AF: 0.641 AC: 26570 AN: 41440

American (AMR) AF: 0.495 AC: 7574 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1803 AN: 3466

East Asian (EAS) AF: 0.561 AC: 2896 AN: 5164

South Asian (SAS) AF: 0.555 AC: 2675 AN: 4818

European-Finnish (FIN) AF: 0.532 AC: 5623 AN: 10562

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33240 AN: 67966

Other (OTH) AF: 0.502 AC: 1059 AN: 2108

Alfa AF: 0.503 Hom.: 86208

Bravo AF: 0.539

Asia WGS AF: 0.516 AC: 1796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.90
DANN	Benign	0.49
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6921502; hg19: chr6-15275305;