9-7155356-A-G

Variant names:

• chr9-7155356-A-G
• rs12001158
• NM_015061.6:c.2782-9882A>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.2782-9882A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,796 control chromosomes in the GnomAD database, including 4,023 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 0.23 (4023 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4C	NM_015061.6	c.2782-9882A>G		intron_variant	Intron 19 of 21	ENST00000381309.8	NP_055876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8	c.2782-9882A>G		intron_variant	Intron 19 of 21	1	NM_015061.6	ENSP00000370710.3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34279 AN: 151676 Hom.: 4018 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.226 AC: 34293 AN: 151796 Hom.: 4023 Cov.: 32 AF XY: 0.222 AC XY: 16490 AN XY: 74186

African (AFR) AF: 0.257 AC: 10618 AN: 41388

American (AMR) AF: 0.260 AC: 3973 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1039 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1368 AN: 5150

South Asian (SAS) AF: 0.122 AC: 586 AN: 4802

European-Finnish (FIN) AF: 0.144 AC: 1519 AN: 10532

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14369 AN: 67886

Other (OTH) AF: 0.257 AC: 543 AN: 2110

Alfa AF: 0.225 Hom.: 11104

Bravo AF: 0.241

Asia WGS AF: 0.178 AC: 620 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.59
PhyloP100		0.085
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: rs12001158; hg19: chr9-7155356;