rs7861972

Variant names:

• chr9-6769692-A-G
• rs7861972
• NM_015061.6:c.-18+11489A>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.-18+11489A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,198 control chromosomes in the GnomAD database, including 1,222 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 0.11 (1222 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• Publications: 4 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 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.-18+11489A>G		intron	N/A	NP_055876.2	Q9H3R0-1
	KDM4C	NM_001353997.3		c.-18+11489A>G		intron	N/A	NP_001340926.1
	KDM4C	NM_001304339.4		c.-18+11489A>G		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.-18+11489A>G		intron	N/A	ENSP00000370710.3	Q9H3R0-1
	KDM4C	ENST00000536108.7	TSL:1	c.-17-23280A>G		intron	N/A	ENSP00000440656.4	Q9H3R0-3
	KDM4C	ENST00000401787.7	TSL:1	c.-18+11489A>G		intron	N/A	ENSP00000383990.3	B0QZ60

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17243 AN: 152080 Hom.: 1220 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0895

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0922

Gnomad FIN AF: 0.0726

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0856

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.113 AC: 17271 AN: 152198 Hom.: 1222 Cov.: 32 AF XY: 0.113 AC XY: 8421 AN XY: 74422

African (AFR) AF: 0.194 AC: 8048 AN: 41504

American (AMR) AF: 0.0893 AC: 1365 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5192

South Asian (SAS) AF: 0.0938 AC: 451 AN: 4810

European-Finnish (FIN) AF: 0.0726 AC: 770 AN: 10602

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0856 AC: 5822 AN: 68014

Other (OTH) AF: 0.106 AC: 224 AN: 2108

Alfa AF: 0.0928 Hom.: 1264

Bravo AF: 0.116

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.44
PhyloP100		-0.058
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7861972;

hg19: chr9-6769692;