rs10975990

chr9-7026716-G-Achr9-7026716-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.2259+10787G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,684 control chromosomes in the GnomAD database, including 21,202 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 0.52 (21202 hom., cov: 30)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM4C	NM_015061.6	c.2259+10787G>A		intron_variant		ENST00000381309.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM4C	ENST00000381309.8	c.2259+10787G>A		intron_variant		1	NM_015061.6	P1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79524 AN: 151566 Hom.: 21159 Cov.: 30

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.525 AC: 79632 AN: 151684 Hom.: 21202 Cov.: 30 AF XY: 0.528 AC XY: 39143 AN XY: 74126

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.548

Gnomad4 SAS AF: 0.699

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.517

Alfa AF: 0.506 Hom.: 11099

Bravo AF: 0.524

Asia WGS AF: 0.641 AC: 2224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.51
Dann	Benign	0.21

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: rs10975990; hg19: chr9-7026716;