9-7155356-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.2782-9882A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,796 control chromosomes in the GnomAD database, including 4,023 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 0.23 (4023 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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 (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM4C	NM_015061.6	c.2782-9882A>G		intron_variant		ENST00000381309.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM4C	ENST00000381309.8	c.2782-9882A>G		intron_variant		1	NM_015061.6	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34279 AN: 151676 Hom.: 4018 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.226 AC: 34293 AN: 151796 Hom.: 4023 Cov.: 32 AF XY: 0.222 AC XY: 16490 AN XY: 74186

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.257

Alfa AF: 0.224 Hom.: 6746

Bravo AF: 0.241

Asia WGS AF: 0.178 AC: 620 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	3.7
Dann	Benign	0.59

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: rs12001158; hg19: chr9-7155356;