rs722628

Variant names:

• chr9-7146888-G-A
• rs722628
• NM_015061.6:c.2782-18350G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-7146888-G-A
• chr9-7146888-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.2782-18350G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,018 control chromosomes in the GnomAD database, including 8,695 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 0.33 (8695 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4C	NM_015061.6	c.2782-18350G>A		intron_variant	Intron 19 of 21	ENST00000381309.8	NP_055876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8	c.2782-18350G>A		intron_variant	Intron 19 of 21	1	NM_015061.6	ENSP00000370710.3

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50527 AN: 151900 Hom.: 8695 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.333 AC: 50551 AN: 152018 Hom.: 8695 Cov.: 32 AF XY: 0.334 AC XY: 24843 AN XY: 74302

African (AFR) AF: 0.250 AC: 10372 AN: 41452

American (AMR) AF: 0.315 AC: 4817 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1322 AN: 3466

East Asian (EAS) AF: 0.513 AC: 2645 AN: 5152

South Asian (SAS) AF: 0.279 AC: 1343 AN: 4818

European-Finnish (FIN) AF: 0.399 AC: 4216 AN: 10556

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24617 AN: 67974

Other (OTH) AF: 0.359 AC: 759 AN: 2112

Alfa AF: 0.353 Hom.: 16257

Bravo AF: 0.328

Asia WGS AF: 0.402 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.75
PhyloP100		-0.88
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: rs722628; hg19: chr9-7146888; COSMIC: COSV67192260;