rs2893923

chr10-63501424-C-T

Variant summary

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

The NM_001318154.2(JMJD1C):c.-379+20314G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 151,960 control chromosomes in the GnomAD database, including 5,948 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 0.27 (5948 hom., cov: 32)
• Consequence: JMJD1C NM_001318154.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.925

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD1C	NM_001318154.2	c.-379+20314G>A		intron_variant
JMJD1C	NM_001322258.2	c.-384+20314G>A		intron_variant
JMJD1C	XM_011539508.3	c.-445+20314G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD1C	ENST00000633035.1	n.113+20314G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41722 AN: 151842 Hom.: 5951 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.275 AC: 41721 AN: 151960 Hom.: 5948 Cov.: 32 AF XY: 0.274 AC XY: 20382 AN XY: 74254

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.339

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.289

Alfa AF: 0.312 Hom.: 11995

Bravo AF: 0.266

Asia WGS AF: 0.287 AC: 1000 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	8.8
Dann	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2893923; hg19: chr10-65261184;