rs10975870

Positions:

• chr9-6880263-A-G
• chr9-6880263-A-T

Variant summary

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

The NM_015061.6(KDM4C):​c.679+202A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 151,466 control chromosomes in the GnomAD database, including 3,962 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 0.20 (3962 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM4C	NM_015061.6	c.679+202A>G		intron_variant		ENST00000381309.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM4C	ENST00000381309.8	c.679+202A>G		intron_variant		1	NM_015061.6	P1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30848 AN: 151348 Hom.: 3962 Cov.: 32

Gnomad AFR AF: 0.0865

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.204 AC: 30840 AN: 151466 Hom.: 3962 Cov.: 32 AF XY: 0.197 AC XY: 14584 AN XY: 73970

Gnomad4 AFR AF: 0.0863

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.00175

Gnomad4 SAS AF: 0.0765

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.249

Alfa AF: 0.247 Hom.: 2915

Bravo AF: 0.204

Asia WGS AF: 0.0410 AC: 145 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	0.20
DANN	Benign	0.48

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: rs10975870; hg19: chr9-6880263;