rs17449018

chr9-7060825-G-Achr9-7060825-G-T

Variant summary

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

The NM_015061.6(KDM4C):c.2424+11625G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,066 control chromosomes in the GnomAD database, including 3,283 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 0.18 (3283 hom., cov: 31)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM4C	NM_015061.6	c.2424+11625G>A		intron_variant		ENST00000381309.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM4C	ENST00000381309.8	c.2424+11625G>A		intron_variant		1	NM_015061.6	P1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26879 AN: 151948 Hom.: 3285 Cov.: 31

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.0870

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.177 AC: 26870 AN: 152066 Hom.: 3283 Cov.: 31 AF XY: 0.174 AC XY: 12923 AN XY: 74344

Gnomad4 AFR AF: 0.0407

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.320

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.0872

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.218

Alfa AF: 0.231 Hom.: 2084

Bravo AF: 0.165

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	2.0
Dann	Benign	0.25

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: rs17449018; hg19: chr9-7060825;