9-6784726-G-C

Variant names:

• chr9-6784726-G-C
• rs10815468
• NM_015061.6:c.-17-8246G>C

Variant summary

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

The NM_015061.6(KDM4C):​c.-17-8246G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,058 control chromosomes in the GnomAD database, including 23,682 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 0.55 (23682 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015061.6. 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
	KDM4C	NM_015061.6	MANE Select	c.-17-8246G>C		intron	N/A	NP_055876.2	Q9H3R0-1
	KDM4C	NM_001353997.3		c.-17-8246G>C		intron	N/A	NP_001340926.1
	KDM4C	NM_001304339.4		c.-17-8246G>C		intron	N/A	NP_001291268.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	ENST00000381309.8	TSL:1 MANE Select	c.-17-8246G>C		intron	N/A	ENSP00000370710.3	Q9H3R0-1
	KDM4C	ENST00000536108.7	TSL:1	c.-17-8246G>C		intron	N/A	ENSP00000440656.4	Q9H3R0-3
	KDM4C	ENST00000401787.7	TSL:1	c.-17-8246G>C		intron	N/A	ENSP00000383990.3	B0QZ60

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83471 AN: 151938 Hom.: 23643 Cov.: 32

Gnomad AFR AF: 0.703

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.550 AC: 83567 AN: 152058 Hom.: 23682 Cov.: 32 AF XY: 0.545 AC XY: 40462 AN XY: 74306

African (AFR) AF: 0.703 AC: 29175 AN: 41488

American (AMR) AF: 0.505 AC: 7716 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1667 AN: 3468

East Asian (EAS) AF: 0.397 AC: 2051 AN: 5162

South Asian (SAS) AF: 0.513 AC: 2470 AN: 4818

European-Finnish (FIN) AF: 0.449 AC: 4752 AN: 10578

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 34004 AN: 67952

Other (OTH) AF: 0.554 AC: 1166 AN: 2106

Alfa AF: 0.363 Hom.: 838

Bravo AF: 0.557

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.5
DANN	Benign	0.60
PhyloP100		0.57
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10815468;

hg19: chr9-6784726;

COSMIC: COSV67184652;