rs7765425

Variant names:

• chr6-15327842-G-A
• rs7765425
• NM_004973.4:c.46-46275G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-15327842-G-A
• chr6-15327842-G-T

Variant summary

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

The NM_004973.4(JARID2):​c.46-46275G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 152,156 control chromosomes in the GnomAD database, including 749 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 0.085 (749 hom., cov: 32)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• 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: 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 (AFR) allele frequency at 95% confidence interval = 0.158 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.46-46275G>A		intron	N/A	NP_004964.2
	JARID2	NM_001267040.1		c.-471-46275G>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.46-46275G>A		intron	N/A	ENSP00000341280.2	Q92833-1
	JARID2	ENST00000853926.1		c.46-46275G>A		intron	N/A	ENSP00000523985.1
	JARID2	ENST00000853927.1		c.46-46275G>A		intron	N/A	ENSP00000523986.1

Frequencies

GnomAD3 genomes AF: 0.0844 AC: 12836 AN: 152038 Hom.: 741 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0534

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0422

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0546

Gnomad OTH AF: 0.0832

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

GnomAD4 genome AF: 0.0846 AC: 12875 AN: 152156 Hom.: 749 Cov.: 32 AF XY: 0.0851 AC XY: 6334 AN XY: 74400

African (AFR) AF: 0.161 AC: 6693 AN: 41462

American (AMR) AF: 0.0528 AC: 808 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3468

East Asian (EAS) AF: 0.0535 AC: 278 AN: 5194

South Asian (SAS) AF: 0.120 AC: 580 AN: 4814

European-Finnish (FIN) AF: 0.0422 AC: 447 AN: 10600

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0547 AC: 3717 AN: 67994

Other (OTH) AF: 0.0856 AC: 181 AN: 2114

Alfa AF: 0.0604 Hom.: 575

Bravo AF: 0.0866

Asia WGS AF: 0.111 AC: 387 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	2.0
DANN	Benign	0.48
PhyloP100		0.0080
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: rs7765425; hg19: chr6-15328073;