6-15461478-G-C

Variant names:

• chr6-15461478-G-C
• rs1474588
• NM_004973.4:c.494-7064G>C

Variant summary

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

The NM_004973.4(JARID2):​c.494-7064G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,994 control chromosomes in the GnomAD database, including 12,499 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 0.40 (12499 hom., cov: 31)
• Consequence: JARID2 NM_004973.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 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.494-7064G>C		intron	N/A	NP_004964.2
	JARID2	NM_001267040.1		c.-23-7064G>C		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.494-7064G>C		intron	N/A	ENSP00000341280.2
	JARID2	ENST00000397311.4	TSL:2	c.-23-7064G>C		intron	N/A	ENSP00000380478.3

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60959 AN: 151876 Hom.: 12480 Cov.: 31

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.401 AC: 61025 AN: 151994 Hom.: 12499 Cov.: 31 AF XY: 0.405 AC XY: 30106 AN XY: 74314

African (AFR) AF: 0.485 AC: 20082 AN: 41442

American (AMR) AF: 0.437 AC: 6685 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1363 AN: 3466

East Asian (EAS) AF: 0.418 AC: 2160 AN: 5162

South Asian (SAS) AF: 0.476 AC: 2292 AN: 4814

European-Finnish (FIN) AF: 0.353 AC: 3724 AN: 10562

Middle Eastern (MID) AF: 0.321 AC: 93 AN: 290

European-Non Finnish (NFE) AF: 0.346 AC: 23478 AN: 67948

Other (OTH) AF: 0.379 AC: 801 AN: 2114

Alfa AF: 0.207 Hom.: 426

Bravo AF: 0.410

Asia WGS AF: 0.476 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.24
DANN	Benign	0.67
PhyloP100		0.037
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: rs1474588; hg19: chr6-15461709;