rs1570513

Variant names:

• chr9-7076586-G-A
• rs1570513
• ENST00000536108.7:c.*135G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-7076586-G-A
• chr9-7076586-G-C
• chr9-7076586-G-T

Variant summary

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

The NM_001146696.2(KDM4C):​c.*135G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 1,481,424 control chromosomes in the GnomAD database, including 412,677 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 0.77 (45933 hom., cov: 32)
  • Exomes 𝑓: 0.74 (366744 hom.)
• Consequence: KDM4C NM_001146696.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340
• Publications: 6 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.836 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146696.2. 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.2425-27099G>A		intron	N/A	NP_055876.2	Q9H3R0-1
	KDM4C	NM_001146696.2		c.*135G>A		3_prime_UTR	Exon 18 of 18	NP_001140168.1	Q9H3R0-4
	KDM4C	NM_001146695.4		c.*135G>A		3_prime_UTR	Exon 18 of 18	NP_001140167.1	Q9H3R0-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	ENST00000536108.7	TSL:1	c.*135G>A		3_prime_UTR	Exon 18 of 18	ENSP00000440656.4	Q9H3R0-3
	KDM4C	ENST00000381309.8	TSL:1 MANE Select	c.2425-27099G>A		intron	N/A	ENSP00000370710.3	Q9H3R0-1
	KDM4C	ENST00000543771.5	TSL:2	c.*135G>A		3_prime_UTR	Exon 18 of 18	ENSP00000445427.1	Q9H3R0-3

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117686 AN: 151958 Hom.: 45867 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.755

GnomAD4 exome AF: 0.742 AC: 986223 AN: 1329348 Hom.: 366744 Cov.: 32 AF XY: 0.741 AC XY: 482221 AN XY: 651060

African (AFR) AF: 0.845 AC: 25440 AN: 30122

American (AMR) AF: 0.843 AC: 25587 AN: 30358

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 13611 AN: 22028

East Asian (EAS) AF: 0.749 AC: 26101 AN: 34842

South Asian (SAS) AF: 0.726 AC: 49247 AN: 67818

European-Finnish (FIN) AF: 0.777 AC: 26228 AN: 33764

Middle Eastern (MID) AF: 0.681 AC: 3674 AN: 5398

European-Non Finnish (NFE) AF: 0.739 AC: 775512 AN: 1049670

Other (OTH) AF: 0.738 AC: 40823 AN: 55348

GnomAD4 genome AF: 0.775 AC: 117820 AN: 152076 Hom.: 45933 Cov.: 32 AF XY: 0.775 AC XY: 57618 AN XY: 74314

African (AFR) AF: 0.843 AC: 34994 AN: 41502

American (AMR) AF: 0.805 AC: 12310 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2142 AN: 3464

East Asian (EAS) AF: 0.746 AC: 3852 AN: 5166

South Asian (SAS) AF: 0.742 AC: 3564 AN: 4804

European-Finnish (FIN) AF: 0.772 AC: 8155 AN: 10564

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50469 AN: 67972

Other (OTH) AF: 0.760 AC: 1606 AN: 2114

Alfa AF: 0.765 Hom.: 17038

Bravo AF: 0.776

Asia WGS AF: 0.793 AC: 2760 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.33
DANN	Benign	0.49
PhyloP100		-0.34
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: rs1570513; hg19: chr9-7076586; COSMIC: COSV67185110;