rs2792226

Variant names:

• chr9-6979382-G-A
• rs2792226
• NM_015061.6:c.922-1543G>A

Variant summary

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

The NM_015061.6(KDM4C):​c.922-1543G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,922 control chromosomes in the GnomAD database, including 13,541 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 0.42 (13541 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4C	NM_015061.6	c.922-1543G>A		intron_variant	Intron 8 of 21	ENST00000381309.8	NP_055876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8	c.922-1543G>A		intron_variant	Intron 8 of 21	1	NM_015061.6	ENSP00000370710.3

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63134 AN: 151804 Hom.: 13521 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.416 AC: 63194 AN: 151922 Hom.: 13541 Cov.: 32 AF XY: 0.413 AC XY: 30675 AN XY: 74226

African (AFR) AF: 0.489 AC: 20249 AN: 41434

American (AMR) AF: 0.368 AC: 5613 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1408 AN: 3472

East Asian (EAS) AF: 0.230 AC: 1186 AN: 5166

South Asian (SAS) AF: 0.261 AC: 1259 AN: 4816

European-Finnish (FIN) AF: 0.453 AC: 4770 AN: 10532

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.403 AC: 27406 AN: 67932

Other (OTH) AF: 0.376 AC: 794 AN: 2112

Alfa AF: 0.399 Hom.: 6727

Bravo AF: 0.417

Asia WGS AF: 0.233 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.4
DANN	Benign	0.50
PhyloP100		0.17
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: rs2792226; hg19: chr9-6979382;