rs7092539

Variant names:

• chr10-63306749-C-T
• rs7092539
• NM_032776.3:c.334-41985G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000399262.7(JMJD1C):​c.334-41985G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 151,990 control chromosomes in the GnomAD database, including 36,189 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 0.66 (36189 hom., cov: 32)
• Consequence: JMJD1C ENST00000399262.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.829
• Publications: 3 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 Gene-Disease associations (from GenCC):

• 22q11.2 deletion syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Illumina
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

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 (NFE) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000399262.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	NM_032776.3	MANE Select	c.334-41985G>A		intron	N/A	NP_116165.1
	JMJD1C	NM_001322252.2		c.333+73569G>A		intron	N/A	NP_001309181.1
	JMJD1C	NM_001318154.2		c.-213-41985G>A		intron	N/A	NP_001305083.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD1C	ENST00000399262.7	TSL:5 MANE Select	c.334-41985G>A		intron	N/A	ENSP00000382204.2
	JMJD1C	ENST00000633035.1	TSL:3	n.279-41985G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101089 AN: 151872 Hom.: 36211 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.807

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.665 AC: 101058 AN: 151990 Hom.: 36189 Cov.: 32 AF XY: 0.667 AC XY: 49589 AN XY: 74310

African (AFR) AF: 0.391 AC: 16204 AN: 41394

American (AMR) AF: 0.605 AC: 9233 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2903 AN: 3468

East Asian (EAS) AF: 0.637 AC: 3293 AN: 5170

South Asian (SAS) AF: 0.733 AC: 3539 AN: 4828

European-Finnish (FIN) AF: 0.826 AC: 8720 AN: 10562

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.807 AC: 54857 AN: 67992

Other (OTH) AF: 0.655 AC: 1379 AN: 2106

Alfa AF: 0.726 Hom.: 5198

Bravo AF: 0.632

Asia WGS AF: 0.612 AC: 2119 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.73
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7092539; hg19: chr10-65066509;