rs2306264

Positions:

• chr10-63194199-C-G
• chr10-63194199-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032776.3(JMJD1C):​c.5734+87G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 830,796 control chromosomes in the GnomAD database, including 28,526 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 0.20 (4045 hom., cov: 32)
  • Exomes 𝑓: 0.25 (24481 hom.)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD1C	NM_032776.3	c.5734+87G>C		intron_variant		ENST00000399262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000399262.7	c.5734+87G>C		intron_variant		5	NM_032776.3

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30633 AN: 151984 Hom.: 4046 Cov.: 32

Gnomad AFR AF: 0.0551

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.0165

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.203

GnomAD4 exome AF: 0.253 AC: 172035 AN: 678694 Hom.: 24481 AF XY: 0.253 AC XY: 92568 AN XY: 365516

Gnomad4 AFR exome AF: 0.0540

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.0153

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.201 AC: 30627 AN: 152102 Hom.: 4045 Cov.: 32 AF XY: 0.201 AC XY: 14958 AN XY: 74348

Gnomad4 AFR AF: 0.0549

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.0166

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.201

Alfa AF: 0.131 Hom.: 258

Bravo AF: 0.188

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.28
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs2306264; hg19: chr10-64953959;