9-6977633-G-A

Position:

• chr9-6977633-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.922-3292G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,018 control chromosomes in the GnomAD database, including 42,222 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 0.74 (42222 hom., cov: 31)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM4C	NM_015061.6	c.922-3292G>A		intron_variant		ENST00000381309.8	NP_055876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8	c.922-3292G>A		intron_variant		1	NM_015061.6	ENSP00000370710.3

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112724 AN: 151900 Hom.: 42181 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.742 AC: 112823 AN: 152018 Hom.: 42222 Cov.: 31 AF XY: 0.738 AC XY: 54794 AN XY: 74272

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.823

Gnomad4 EAS AF: 0.588

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.760

Alfa AF: 0.743 Hom.: 21384

Bravo AF: 0.737

Asia WGS AF: 0.586 AC: 2040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.31

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: rs1340513; hg19: chr9-6977633;