rs16925187

Variant names:

• chr9-7043455-C-G
• rs16925187
• NM_015061.6:c.2260-3407C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-7043455-C-G
• chr9-7043455-C-T

Variant summary

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

The NM_015061.6(KDM4C):​c.2260-3407C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 152,002 control chromosomes in the GnomAD database, including 210 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 0.050 (210 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.873
• Publications: 5 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 (SAS) allele frequency at 95% confidence interval = 0.0809 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015061.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	NM_015061.6	MANE Select	c.2260-3407C>G		intron	N/A	NP_055876.2
	KDM4C	NM_001353997.3		c.2260-3407C>G		intron	N/A	NP_001340926.1
	KDM4C	NM_001304339.4		c.2260-3407C>G		intron	N/A	NP_001291268.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	ENST00000381309.8	TSL:1 MANE Select	c.2260-3407C>G		intron	N/A	ENSP00000370710.3
	KDM4C	ENST00000536108.7	TSL:1	c.2260-3407C>G		intron	N/A	ENSP00000440656.4
	KDM4C	ENST00000381306.7	TSL:2	c.2260-3407C>G		intron	N/A	ENSP00000370707.3

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7659 AN: 151884 Hom.: 211 Cov.: 32

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.0840

Gnomad SAS AF: 0.0871

Gnomad FIN AF: 0.0616

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.0422

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

GnomAD4 genome AF: 0.0504 AC: 7666 AN: 152002 Hom.: 210 Cov.: 32 AF XY: 0.0516 AC XY: 3837 AN XY: 74322

African (AFR) AF: 0.0596 AC: 2471 AN: 41492

American (AMR) AF: 0.0285 AC: 435 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3464

East Asian (EAS) AF: 0.0836 AC: 431 AN: 5154

South Asian (SAS) AF: 0.0878 AC: 423 AN: 4816

European-Finnish (FIN) AF: 0.0616 AC: 653 AN: 10594

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0443 AC: 3008 AN: 67926

Other (OTH) AF: 0.0423 AC: 89 AN: 2106

Alfa AF: 0.0255 Hom.: 14

Bravo AF: 0.0466

Asia WGS AF: 0.0770 AC: 271 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.73
PhyloP100		0.87
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: rs16925187; hg19: chr9-7043455;