rs2893923

Variant names:

• chr10-63501424-C-T
• rs2893923
• NM_001318154.2:c.-379+20314G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 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-AS1 (HGNC:28222): (JMJD1C antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318154.2. 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_001318154.2		c.-379+20314G>A		intron	N/A	NP_001305083.1	Q15652-3
	JMJD1C	NM_001322258.2		c.-384+20314G>A		intron	N/A	NP_001309187.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000633035.1	TSL:3	n.113+20314G>A		intron	N/A
	JMJD1C-AS1	ENST00000719935.1		n.250-1369C>T		intron	N/A

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

African (AFR) AF: 0.198 AC: 8183 AN: 41414

American (AMR) AF: 0.233 AC: 3559 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1246 AN: 3466

East Asian (EAS) AF: 0.339 AC: 1754 AN: 5174

South Asian (SAS) AF: 0.256 AC: 1232 AN: 4814

European-Finnish (FIN) AF: 0.308 AC: 3253 AN: 10552

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21540 AN: 67938

Other (OTH) AF: 0.289 AC: 609 AN: 2106

Alfa AF: 0.306 Hom.: 25640

Bravo AF: 0.266

Asia WGS AF: 0.287 AC: 1000 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.8
DANN	Benign	0.70
PhyloP100		0.93

Splicing

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

Other links and lift over

dbSNP: rs2893923; hg19: chr10-65261184;