rs1340513

Variant names:

• chr9-6977633-G-A
• rs1340513
• NM_015061.6:c.922-3292G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KDM4C	NM_015061.6	c.922-3292G>A		intron_variant	Intron 8 of 21	ENST00000381309.8	NP_055876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8	c.922-3292G>A		intron_variant	Intron 8 of 21	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

African (AFR) AF: 0.762 AC: 31627 AN: 41482

American (AMR) AF: 0.668 AC: 10182 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2856 AN: 3472

East Asian (EAS) AF: 0.588 AC: 3012 AN: 5124

South Asian (SAS) AF: 0.543 AC: 2613 AN: 4810

European-Finnish (FIN) AF: 0.810 AC: 8559 AN: 10568

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51470 AN: 67998

Other (OTH) AF: 0.760 AC: 1601 AN: 2106

Alfa AF: 0.744 Hom.: 23798

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
PhyloP100		-0.96
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1340513; hg19: chr9-6977633;