rs4400684

Positions:

• chr10-63252927-A-G
• chr10-63252927-A-T

Variant summary

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

The NM_032776.3(JMJD1C):​c.447+11724T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,118 control chromosomes in the GnomAD database, including 14,415 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 (14415 hom., cov: 33)
• Consequence: JMJD1C NM_032776.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD1C	NM_032776.3	c.447+11724T>C		intron_variant		ENST00000399262.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000399262.7	c.447+11724T>C		intron_variant		5	NM_032776.3

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64778 AN: 152002 Hom.: 14428 Cov.: 33

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.426 AC: 64749 AN: 152118 Hom.: 14415 Cov.: 33 AF XY: 0.425 AC XY: 31612 AN XY: 74354

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.422

Alfa AF: 0.346 Hom.: 1052

Bravo AF: 0.404

Asia WGS AF: 0.409 AC: 1421 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.45
DANN	Benign	0.60

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: rs4400684; hg19: chr10-65012687;