rs1570513

chr9-7076586-G-Achr9-7076586-G-C

Variant summary

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

The NM_015061.6(KDM4C):c.2425-27099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,481,424 control chromosomes in the GnomAD database, including 412,677 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 0.77 (45933 hom., cov: 32)
  • Exomes 𝑓: 0.74 (366744 hom.)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM4C	NM_015061.6	c.2425-27099G>A		intron_variant		ENST00000381309.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM4C	ENST00000381309.8	c.2425-27099G>A		intron_variant		1	NM_015061.6	P1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117686 AN: 151958 Hom.: 45867 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.755

GnomAD4 exome AF: 0.742 AC: 986223 AN: 1329348 Hom.: 366744 Cov.: 32 AF XY: 0.741 AC XY: 482221 AN XY: 651060

Gnomad4 AFR exome AF: 0.845

Gnomad4 AMR exome AF: 0.843

Gnomad4 ASJ exome AF: 0.618

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.726

Gnomad4 FIN exome AF: 0.777

Gnomad4 NFE exome AF: 0.739

Gnomad4 OTH exome AF: 0.738

GnomAD4 genome AF: 0.775 AC: 117820 AN: 152076 Hom.: 45933 Cov.: 32 AF XY: 0.775 AC XY: 57618 AN XY: 74314

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.618

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.760

Alfa AF: 0.772 Hom.: 9588

Bravo AF: 0.776

Asia WGS AF: 0.793 AC: 2760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.33
Dann	Benign	0.49

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: rs1570513; hg19: chr9-7076586; COSMIC: COSV67185110;