rs17449018

Variant names:

• chr9-7060825-G-A
• rs17449018
• NM_015061.6:c.2424+11625G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-7060825-G-A
• chr9-7060825-G-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.2424+11625G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,066 control chromosomes in the GnomAD database, including 3,283 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 (3283 hom., cov: 31)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.253 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.2424+11625G>A		intron	N/A	NP_055876.2
	KDM4C	NM_001353997.3		c.2424+11625G>A		intron	N/A	NP_001340926.1
	KDM4C	NM_001304339.4		c.2424+11625G>A		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.2424+11625G>A		intron	N/A	ENSP00000370710.3
	KDM4C	ENST00000536108.7	TSL:1	c.2424+11625G>A		intron	N/A	ENSP00000440656.4
	KDM4C	ENST00000381306.7	TSL:2	c.2424+11625G>A		intron	N/A	ENSP00000370707.3

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26879 AN: 151948 Hom.: 3285 Cov.: 31

Gnomad AFR AF: 0.0408

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.0870

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.177 AC: 26870 AN: 152066 Hom.: 3283 Cov.: 31 AF XY: 0.174 AC XY: 12923 AN XY: 74344

African (AFR) AF: 0.0407 AC: 1689 AN: 41532

American (AMR) AF: 0.172 AC: 2624 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1107 AN: 3462

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5170

South Asian (SAS) AF: 0.0872 AC: 420 AN: 4814

European-Finnish (FIN) AF: 0.269 AC: 2841 AN: 10542

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17437 AN: 67982

Other (OTH) AF: 0.218 AC: 461 AN: 2114

Alfa AF: 0.233 Hom.: 2379

Bravo AF: 0.165

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.0
DANN	Benign	0.25
PhyloP100		-0.38
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: rs17449018; hg19: chr9-7060825;