9-7065141-A-G

Variant names:

• chr9-7065141-A-G
• rs4742299
• NM_015061.6:c.2424+15941A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015061.6(KDM4C):​c.2424+15941A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,138 control chromosomes in the GnomAD database, including 3,002 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 0.18 (3002 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4C	NM_015061.6	c.2424+15941A>G		intron_variant	Intron 17 of 21	ENST00000381309.8	NP_055876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8	c.2424+15941A>G		intron_variant	Intron 17 of 21	1	NM_015061.6	ENSP00000370710.3

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27346 AN: 152018 Hom.: 3005 Cov.: 32

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.180 AC: 27356 AN: 152138 Hom.: 3002 Cov.: 32 AF XY: 0.185 AC XY: 13786 AN XY: 74386

African (AFR) AF: 0.0937 AC: 3891 AN: 41532

American (AMR) AF: 0.288 AC: 4396 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 640 AN: 3470

East Asian (EAS) AF: 0.285 AC: 1474 AN: 5172

South Asian (SAS) AF: 0.419 AC: 2019 AN: 4814

European-Finnish (FIN) AF: 0.135 AC: 1425 AN: 10572

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12851 AN: 67982

Other (OTH) AF: 0.183 AC: 386 AN: 2114

Alfa AF: 0.192 Hom.: 12399

Bravo AF: 0.180

Asia WGS AF: 0.340 AC: 1180 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.51
DANN	Benign	0.20
PhyloP100		-2.0
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: rs4742299; hg19: chr9-7065141;