rs4379723

chr10-63203689-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD1C	NM_032776.3	c.5074+2906A>G		intron_variant		ENST00000399262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000399262.7	c.5074+2906A>G		intron_variant		5	NM_032776.3
JMJD1C	ENST00000542921.5	c.4528+2906A>G		intron_variant		1		P1
JMJD1C	ENST00000402544.5	n.5046+2906A>G		intron_variant, non_coding_transcript_variant		1
JMJD1C	ENST00000327520.7	c.1131+2906A>G		intron_variant		2

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

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.291

Gnomad4 ASJ exome AF: 0.573

Gnomad4 EAS exome AF: 0.358

Gnomad4 SAS exome AF: 0.541

Gnomad4 FIN exome AF: 0.544

Gnomad4 NFE exome AF: 0.472

Gnomad4 OTH exome AF: 0.453

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

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.425

Alfa AF: 0.477 Hom.: 9305

Bravo AF: 0.405

Asia WGS AF: 0.420 AC: 1452 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.27
Dann	Benign	0.58

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: rs4379723; hg19: chr10-64963449;