Genetic Variant KDM4C:c.2994+852A>G (chr9-7170742-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_015061.6(KDM4C):c.2994+852A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 982,140 control chromosomes in the GnomAD database, including 956 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 0.057 ( 323 hom., cov: 32)

Exomes 𝑓: 0.036 ( 633 hom. )

Consequence

KDM4C
NM_015061.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0390

Publications

4 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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0979 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KDM4C	NM_015061.6	MANE Select	c.2994+852A>G	intron	N/A	NP_055876.2
KDM4C	NM_001353997.3		c.3093+852A>G	intron	N/A	NP_001340926.1
KDM4C	NM_001304339.4		c.2994+852A>G	intron	N/A	NP_001291268.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KDM4C	ENST00000381309.8	TSL:1 MANE Select	c.2994+852A>G	intron	N/A	ENSP00000370710.3
KDM4C	ENST00000381306.7	TSL:2	c.*702A>G	3_prime_UTR	Exon 21 of 21	ENSP00000370707.3
KDM4C	ENST00000428870.6	TSL:2	c.2055+852A>G	intron	N/A	ENSP00000405739.2

Frequencies

GnomAD3 genomes

AF:

0.0571

AC:

8675

AN:

151976

Hom.:

320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.100

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0400

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.0455

Gnomad SAS

AF:

0.0930

Gnomad FIN

AF:

0.0511

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0338

Gnomad OTH

AF:

0.0617

GnomAD4 exome

AF:

0.0359

AC:

29760

AN:

830046

Hom.:

633

Cov.:

AF XY:

0.0360

AC XY:

13802

AN XY:

383416

show subpopulations

African (AFR)

AF:

0.105

AC:

1646

AN:

15706

American (AMR)

AF:

0.0265

AC:

AN:

980

Ashkenazi Jewish (ASJ)

AF:

0.0556

AC:

285

AN:

5126

East Asian (EAS)

AF:

0.0377

AC:

136

AN:

3612

South Asian (SAS)

AF:

0.0978

AC:

1601

AN:

16368

European-Finnish (FIN)

AF:

0.0365

AC:

AN:

274

Middle Eastern (MID)

AF:

0.0829

AC:

134

AN:

1616

European-Non Finnish (NFE)

AF:

0.0325

AC:

24693

AN:

759188

Other (OTH)

AF:

0.0452

AC:

1229

AN:

27176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

1215

2430

3644

4859

6074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1356

2712

4068

5424

6780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0572

AC:

8699

AN:

152094

Hom.:

323

Cov.:

AF XY:

0.0581

AC XY:

4321

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.100

AC:

4161

AN:

41442

American (AMR)

AF:

0.0399

AC:

610

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0510

AC:

177

AN:

3472

East Asian (EAS)

AF:

0.0458

AC:

237

AN:

5180

South Asian (SAS)

AF:

0.0927

AC:

447

AN:

4824

European-Finnish (FIN)

AF:

0.0511

AC:

540

AN:

10566

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0338

AC:

2300

AN:

68010

Other (OTH)

AF:

0.0615

AC:

130

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

390

780

1169

1559

1949

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0393

Hom.:

234

Bravo

AF:

0.0570

Asia WGS

AF:

0.0750

AC:

264

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.75

(source)

DANN

Benign

0.52

PhyloP100

-0.039

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over