rs7861972

chr9-6769692-A-G

Variant summary

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

The NM_015061.6(KDM4C):c.-18+11489A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,198 control chromosomes in the GnomAD database, including 1,222 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 0.11 (1222 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM4C	NM_015061.6	c.-18+11489A>G		intron_variant		ENST00000381309.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM4C	ENST00000381309.8	c.-18+11489A>G		intron_variant		1	NM_015061.6	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17243 AN: 152080 Hom.: 1220 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0895

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0922

Gnomad FIN AF: 0.0726

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0856

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.113 AC: 17271 AN: 152198 Hom.: 1222 Cov.: 32 AF XY: 0.113 AC XY: 8421 AN XY: 74422

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0893

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0938

Gnomad4 FIN AF: 0.0726

Gnomad4 NFE AF: 0.0856

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0913 Hom.: 902

Bravo AF: 0.116

Asia WGS AF: 0.0500 AC: 174 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	2.1
Dann	Benign	0.44

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: rs7861972; hg19: chr9-6769692;