rs16925187

chr9-7043455-C-Gchr9-7043455-C-T

Variant summary

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

The NM_015061.6(KDM4C):c.2260-3407C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 152,002 control chromosomes in the GnomAD database, including 210 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 0.050 (210 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.873

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM4C	NM_015061.6	c.2260-3407C>G		intron_variant		ENST00000381309.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM4C	ENST00000381309.8	c.2260-3407C>G		intron_variant		1	NM_015061.6	P1

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7659 AN: 151884 Hom.: 211 Cov.: 32

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.0840

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.0616

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.0422

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

GnomAD4 genome AF: 0.0504 AC: 7666 AN: 152002 Hom.: 210 Cov.: 32 AF XY: 0.0516 AC XY: 3837 AN XY: 74322

Gnomad4 AFR AF: 0.0596

Gnomad4 AMR AF: 0.0285

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.0836

Gnomad4 SAS AF: 0.0878

Gnomad4 FIN AF: 0.0616

Gnomad4 NFE AF: 0.0443

Gnomad4 OTH AF: 0.0423

Alfa AF: 0.0255 Hom.: 14

Bravo AF: 0.0466

Asia WGS AF: 0.0770 AC: 271 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	2.5
Dann	Benign	0.73

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: rs16925187; hg19: chr9-7043455;