rs4379723

Variant names:

• chr10-63203689-T-C
• rs4379723
• NM_032776.3:c.5074+2906A>G

Variant summary

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

The NM_032776.3(JMJD1C):​c.5074+2906A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 979,990 control chromosomes in the GnomAD database, including 106,583 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 0.43 (14531 hom., cov: 32)
  • Exomes 𝑓: 0.47 (92052 hom.)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 30 publications found

Genes affected

JMJD1C (HGNC:12313): (jumonji domain containing 1C) The protein encoded by this gene interacts with thyroid hormone receptors and contains a jumonji domain. It is a candidate histone demethylase and is thought to be a coactivator for key transcription factors. It plays a role in the DNA-damage response pathway by demethylating the mediator of DNA damage checkpoint 1 (MDC1) protein, and is required for the survival of acute myeloid leukemia. Mutations in this gene are associated with Rett syndrome and intellectual disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

JMJD1C Gene-Disease associations (from GenCC):

• 22q11.2 deletion syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032776.3. 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
	JMJD1C	NM_032776.3	MANE Select	c.5074+2906A>G		intron	N/A	NP_116165.1	Q15652-1
	JMJD1C	NM_001322252.2		c.4960+2906A>G		intron	N/A	NP_001309181.1
	JMJD1C	NM_001282948.2		c.4528+2906A>G		intron	N/A	NP_001269877.1	Q15652-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.5074+2906A>G		intron	N/A	ENSP00000382204.2	Q15652-1
	JMJD1C	ENST00000542921.5	TSL:1	c.4528+2906A>G		intron	N/A	ENSP00000444682.1	Q15652-3
	JMJD1C	ENST00000402544.5	TSL:1	n.5046+2906A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.428 AC: 65013 AN: 151742 Hom.: 14545 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.470 AC: 388889 AN: 828132 Hom.: 92052 Cov.: 28 AF XY: 0.470 AC XY: 179833 AN XY: 382564

African (AFR) AF: 0.317 AC: 4986 AN: 15708

American (AMR) AF: 0.291 AC: 286 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 2934 AN: 5116

East Asian (EAS) AF: 0.358 AC: 1295 AN: 3618

South Asian (SAS) AF: 0.541 AC: 8855 AN: 16356

European-Finnish (FIN) AF: 0.544 AC: 149 AN: 274

Middle Eastern (MID) AF: 0.427 AC: 688 AN: 1612

European-Non Finnish (NFE) AF: 0.472 AC: 357409 AN: 757338

Other (OTH) AF: 0.453 AC: 12287 AN: 27128

GnomAD4 genome AF: 0.428 AC: 64985 AN: 151858 Hom.: 14531 Cov.: 32 AF XY: 0.428 AC XY: 31764 AN XY: 74214

African (AFR) AF: 0.327 AC: 13539 AN: 41380

American (AMR) AF: 0.345 AC: 5262 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2038 AN: 3472

East Asian (EAS) AF: 0.358 AC: 1852 AN: 5180

South Asian (SAS) AF: 0.535 AC: 2582 AN: 4824

European-Finnish (FIN) AF: 0.474 AC: 4984 AN: 10510

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.488 AC: 33136 AN: 67922

Other (OTH) AF: 0.425 AC: 896 AN: 2110

Alfa AF: 0.459 Hom.: 11106

Bravo AF: 0.405

Asia WGS AF: 0.420 AC: 1452 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.27
DANN	Benign	0.58
PhyloP100		-1.0
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: rs4379723; hg19: chr10-64963449;