rs10975869

Variant names:

• chr9-6874688-A-G
• rs10975869
• NM_015061.6:c.630-5324A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-6874688-A-G
• chr9-6874688-A-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.630-5324A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,104 control chromosomes in the GnomAD database, including 4,214 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 0.21 (4214 hom., cov: 31)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4C	NM_015061.6	c.630-5324A>G		intron_variant	Intron 5 of 21	ENST00000381309.8	NP_055876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8	c.630-5324A>G		intron_variant	Intron 5 of 21	1	NM_015061.6	ENSP00000370710.3

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32588 AN: 151986 Hom.: 4214 Cov.: 31

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0774

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.214 AC: 32586 AN: 152104 Hom.: 4214 Cov.: 31 AF XY: 0.208 AC XY: 15453 AN XY: 74376

African (AFR) AF: 0.112 AC: 4656 AN: 41506

American (AMR) AF: 0.219 AC: 3344 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1197 AN: 3470

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.0778 AC: 375 AN: 4818

European-Finnish (FIN) AF: 0.216 AC: 2284 AN: 10558

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19855 AN: 67980

Other (OTH) AF: 0.259 AC: 548 AN: 2112

Alfa AF: 0.264 Hom.: 1145

Bravo AF: 0.215

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		-0.31
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: rs10975869; hg19: chr9-6874688;