dbSNP rs1570513: KDM4C:c.*135G>A (chr9-7076586-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.340

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 made for transcript

Verdict is Benign. Variant got -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

Gnomad4 AFR exome

AF:

0.845

Gnomad4 AMR exome

AF:

0.843

Gnomad4 ASJ exome

AF:

0.618

Gnomad4 EAS exome

AF:

0.749

Gnomad4 SAS exome

AF:

0.726

Gnomad4 FIN exome

AF:

0.777

Gnomad4 NFE exome

AF:

0.739

Gnomad4 OTH exome

AF:

0.738

GnomAD4 genome

AF:

0.775

AC:

117820

AN:

152076

Hom.:

45933

Cov.:

AF XY:

0.775

AC XY:

57618

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.843

Gnomad4 AMR

AF:

0.805

Gnomad4 ASJ

AF:

0.618

Gnomad4 EAS

AF:

0.746

Gnomad4 SAS

AF:

0.742

Gnomad4 FIN

AF:

0.772

Gnomad4 NFE

AF:

0.742

Gnomad4 OTH

AF:

0.760

Alfa

AF:

0.772

Hom.:

9588

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

DANN

Benign

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over