rs1407856

Variant names:

• chr9-7046901-C-G
• rs1407856
• NM_015061.6:c.2299C>G

Variant summary

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

The NM_015061.6(KDM4C):​c.2299C>G​(p.Gln767Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,594,768 control chromosomes in the GnomAD database, including 32,250 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2538 hom., cov: 32)
  • Exomes 𝑓: 0.19 (29712 hom.)
• Consequence: KDM4C NM_015061.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 25 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 (MetaRNN=0.002591759).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4C	NM_015061.6	c.2299C>G	p.Gln767Glu	missense_variant	Exon 16 of 22	ENST00000381309.8	NP_055876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8	c.2299C>G	p.Gln767Glu	missense_variant	Exon 16 of 22	1	NM_015061.6	ENSP00000370710.3

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23902 AN: 151890 Hom.: 2535 Cov.: 32

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.160

GnomAD2 exomes AF: 0.219 AC: 54756 AN: 250218 AF XY: 0.224

Gnomad AFR exome AF: 0.0473

Gnomad AMR exome AF: 0.345

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.277

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.191 AC: 274950 AN: 1442760 Hom.: 29712 Cov.: 28 AF XY: 0.196 AC XY: 140818 AN XY: 718734

African (AFR) AF: 0.0467 AC: 1552 AN: 33222

American (AMR) AF: 0.333 AC: 14786 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 3926 AN: 25948

East Asian (EAS) AF: 0.239 AC: 9460 AN: 39540

South Asian (SAS) AF: 0.378 AC: 32307 AN: 85374

European-Finnish (FIN) AF: 0.127 AC: 6766 AN: 53368

Middle Eastern (MID) AF: 0.148 AC: 850 AN: 5736

European-Non Finnish (NFE) AF: 0.177 AC: 193835 AN: 1095432

Other (OTH) AF: 0.192 AC: 11468 AN: 59676

GnomAD4 genome AF: 0.157 AC: 23911 AN: 152008 Hom.: 2538 Cov.: 32 AF XY: 0.162 AC XY: 12050 AN XY: 74312

African (AFR) AF: 0.0558 AC: 2318 AN: 41520

American (AMR) AF: 0.271 AC: 4130 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3466

East Asian (EAS) AF: 0.267 AC: 1378 AN: 5156

South Asian (SAS) AF: 0.399 AC: 1918 AN: 4812

European-Finnish (FIN) AF: 0.114 AC: 1212 AN: 10598

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11842 AN: 67922

Other (OTH) AF: 0.163 AC: 344 AN: 2110

Alfa AF: 0.174 Hom.: 1869

Bravo AF: 0.159

TwinsUK AF: 0.191 AC: 710

ALSPAC AF: 0.180 AC: 693

ESP6500AA AF: 0.0529 AC: 233

ESP6500EA AF: 0.177 AC: 1519

ExAC AF: 0.215 AC: 26067

Asia WGS AF: 0.311 AC: 1077 AN: 3478

EpiCase AF: 0.173

EpiControl AF: 0.172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.012	.;.;T;.;T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.55	T;T;T;T;T;T
MetaRNN	Benign	0.0026	T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	.;L;L;L;.;.
PhyloP100		2.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.93	.;N;N;N;N;N
REVEL	Benign	0.037
Sift	Benign	0.31	.;T;T;T;T;T
Sift4G	Benign	0.42	.;T;T;T;T;T
Polyphen		0.0010, 0.0	.;B;B;.;.;.
Vest4		0.035, 0.056, 0.092, 0.087
MPC		0.042
ClinPred		0.0057	T
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.46
Mutation Taster		=99/1	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: rs1407856; hg19: chr9-7046901; COSMIC: COSV67186826; COSMIC: COSV67186826;