rs2381545

Positions:

• chr9-7072038-A-G

Variant summary

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

The NM_015061.6(KDM4C):​c.2424+22838A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,150 control chromosomes in the GnomAD database, including 46,298 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 0.78 (46298 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

Genes affected

KDM4C (HGNC:17071): (lysine demethylase 4C) This gene is a member of the Jumonji domain 2 (JMJD2) family. The encoded protein is a trimethylation-specific demethylase, and converts specific trimethylated histone residues to the dimethylated form. This enzymatic action regulates gene expression and chromosome segregation. Chromosomal aberrations and changes in expression of this gene may be found in tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM4C	NM_015061.6	c.2424+22838A>G		intron_variant		ENST00000381309.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM4C	ENST00000381309.8	c.2424+22838A>G		intron_variant		1	NM_015061.6	P1

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118254 AN: 152032 Hom.: 46256 Cov.: 32

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.778 AC: 118356 AN: 152150 Hom.: 46298 Cov.: 32 AF XY: 0.778 AC XY: 57890 AN XY: 74366

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.799

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.776

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.763

Alfa AF: 0.775 Hom.: 13064

Bravo AF: 0.777

Asia WGS AF: 0.798 AC: 2777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2381545; hg19: chr9-7072038;