9-6978321-A-G

Variant names:

• chr9-6978321-A-G
• rs16925027
• NM_015061.6:c.922-2604A>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.922-2604A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 150,120 control chromosomes in the GnomAD database, including 3,482 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 0.21 (3482 hom., cov: 33)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• Publications: 3 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]

ENSG00000224972 (HGNC:):

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 = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4C	NM_015061.6	c.922-2604A>G		intron_variant	Intron 8 of 21	ENST00000381309.8	NP_055876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8	c.922-2604A>G		intron_variant	Intron 8 of 21	1	NM_015061.6	ENSP00000370710.3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31473 AN: 150004 Hom.: 3474 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0938

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.210 AC: 31498 AN: 150120 Hom.: 3482 Cov.: 33 AF XY: 0.208 AC XY: 15226 AN XY: 73334

African (AFR) AF: 0.220 AC: 9075 AN: 41340

American (AMR) AF: 0.135 AC: 2021 AN: 14998

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 673 AN: 3444

East Asian (EAS) AF: 0.0938 AC: 441 AN: 4704

South Asian (SAS) AF: 0.142 AC: 655 AN: 4608

European-Finnish (FIN) AF: 0.247 AC: 2578 AN: 10432

Middle Eastern (MID) AF: 0.156 AC: 45 AN: 288

European-Non Finnish (NFE) AF: 0.230 AC: 15453 AN: 67316

Other (OTH) AF: 0.185 AC: 385 AN: 2084

Alfa AF: 0.209 Hom.: 6752

Bravo AF: 0.199

Asia WGS AF: 0.110 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.2
DANN	Benign	0.66
PhyloP100		-0.24
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: rs16925027; hg19: chr9-6978321;