9-7150997-T-C

Variant names:

• chr9-7150997-T-C
• rs913581
• NM_015061.6:c.2782-14241T>C

Variant summary

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

The NM_015061.6(KDM4C):​c.2782-14241T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,172 control chromosomes in the GnomAD database, including 54,559 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 0.84 (54559 hom., cov: 31)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	NM_015061.6	MANE Select	c.2782-14241T>C		intron	N/A	NP_055876.2	Q9H3R0-1
	KDM4C	NM_001353997.3		c.2881-14241T>C		intron	N/A	NP_001340926.1
	KDM4C	NM_001304339.4		c.2782-14241T>C		intron	N/A	NP_001291268.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	ENST00000381309.8	TSL:1 MANE Select	c.2782-14241T>C		intron	N/A	ENSP00000370710.3	Q9H3R0-1
	KDM4C	ENST00000948679.1		c.2782-14241T>C		intron	N/A	ENSP00000618738.1
	KDM4C	ENST00000948683.1		c.2782-14241T>C		intron	N/A	ENSP00000618742.1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128412 AN: 152054 Hom.: 54505 Cov.: 31

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.845 AC: 128527 AN: 152172 Hom.: 54559 Cov.: 31 AF XY: 0.844 AC XY: 62777 AN XY: 74416

African (AFR) AF: 0.908 AC: 37681 AN: 41508

American (AMR) AF: 0.757 AC: 11569 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2820 AN: 3470

East Asian (EAS) AF: 0.791 AC: 4084 AN: 5164

South Asian (SAS) AF: 0.702 AC: 3386 AN: 4824

European-Finnish (FIN) AF: 0.918 AC: 9737 AN: 10610

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56557 AN: 67990

Other (OTH) AF: 0.831 AC: 1759 AN: 2116

Alfa AF: 0.831 Hom.: 222927

Bravo AF: 0.838

Asia WGS AF: 0.758 AC: 2637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.0
DANN	Benign	0.33
PhyloP100		-0.083
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: rs913581; hg19: chr9-7150997;