rs2792226

Positions:

• chr9-6979382-G-A

Variant summary

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

The NM_015061.6(KDM4C):​c.922-1543G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,922 control chromosomes in the GnomAD database, including 13,541 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 0.42 (13541 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM4C	NM_015061.6	c.922-1543G>A		intron_variant		ENST00000381309.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM4C	ENST00000381309.8	c.922-1543G>A		intron_variant		1	NM_015061.6	P1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63134 AN: 151804 Hom.: 13521 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.416 AC: 63194 AN: 151922 Hom.: 13541 Cov.: 32 AF XY: 0.413 AC XY: 30675 AN XY: 74226

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.368

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.376

Alfa AF: 0.399 Hom.: 6116

Bravo AF: 0.417

Asia WGS AF: 0.233 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.50

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: rs2792226; hg19: chr9-6979382;