rs9296975

Variant names:

• chr6-15515276-C-A
• rs9296975
• NM_004973.4:c.3450+1854C>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.3450+1854C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 152,044 control chromosomes in the GnomAD database, including 517 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 0.078 (517 hom., cov: 31)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JARID2	NM_004973.4	c.3450+1854C>A		intron_variant	Intron 16 of 17	ENST00000341776.7	NP_004964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JARID2	ENST00000341776.7	c.3450+1854C>A		intron_variant	Intron 16 of 17	1	NM_004973.4	ENSP00000341280.2
JARID2	ENST00000397311.4	c.2934+1854C>A		intron_variant	Intron 16 of 17	2		ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11828 AN: 151926 Hom.: 520 Cov.: 31

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0430

Gnomad FIN AF: 0.0570

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0627

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

GnomAD4 genome AF: 0.0778 AC: 11834 AN: 152044 Hom.: 517 Cov.: 31 AF XY: 0.0766 AC XY: 5689 AN XY: 74298

African (AFR) AF: 0.114 AC: 4736 AN: 41456

American (AMR) AF: 0.0963 AC: 1471 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0524 AC: 182 AN: 3470

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5174

South Asian (SAS) AF: 0.0430 AC: 207 AN: 4812

European-Finnish (FIN) AF: 0.0570 AC: 603 AN: 10572

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0649 AC: 4408 AN: 67970

Other (OTH) AF: 0.0621 AC: 131 AN: 2110

Alfa AF: 0.0872 Hom.: 250

Bravo AF: 0.0836

Asia WGS AF: 0.0280 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.70
PhyloP100		-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: rs9296975; hg19: chr6-15515507;