Genetic Variant KDM4C:c.*135G>A (chr9-7076586-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000536108.7(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
ENST00000536108.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.340

Publications

6 publications found

Variant links:

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]

KDM4C links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4C	NM_015061.6 link	c.2425-27099G>A		intron_variant	Intron 17 of 21	ENST00000381309.8	NP_055876.2	Q9H3R0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8 link	c.2425-27099G>A		intron_variant	Intron 17 of 21	1	NM_015061.6	ENSP00000370710.3		Q9H3R0-1

Frequencies

GnomAD3 genomes

AF:

0.774

AC:

117686

AN:

151958

Hom.:

45867

Cov.:

show subpopulations

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.:

AF XY:

0.741

AC XY:

482221

AN XY:

651060

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

11335

22671

34006

45342

56677

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.775

AC:

117820

AN:

152076

Hom.:

45933

Cov.:

AF XY:

0.775

AC XY:

57618

AN XY:

74314

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1323

2646

3968

5291

6614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.33

(source)

DANN

Benign

0.49

PhyloP100

-0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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chr9-7076586-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over