rs4742269

Variant names:

• chr9-6849317-G-A
• rs4742269
• NM_015061.6:c.436-190G>A

Variant summary

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

The NM_015061.6(KDM4C):​c.436-190G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,232 control chromosomes in the GnomAD database, including 1,212 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 0.11 (1212 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4C	NM_015061.6	c.436-190G>A		intron_variant	Intron 4 of 21	ENST00000381309.8	NP_055876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8	c.436-190G>A		intron_variant	Intron 4 of 21	1	NM_015061.6	ENSP00000370710.3

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16212 AN: 152114 Hom.: 1208 Cov.: 32

Gnomad AFR AF: 0.189

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0513

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0195

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0560

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.107 AC: 16235 AN: 152232 Hom.: 1212 Cov.: 32 AF XY: 0.108 AC XY: 8028 AN XY: 74442

African (AFR) AF: 0.189 AC: 7853 AN: 41508

American (AMR) AF: 0.157 AC: 2398 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 178 AN: 3470

East Asian (EAS) AF: 0.121 AC: 628 AN: 5194

South Asian (SAS) AF: 0.180 AC: 866 AN: 4824

European-Finnish (FIN) AF: 0.0195 AC: 207 AN: 10606

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0560 AC: 3810 AN: 68016

Other (OTH) AF: 0.107 AC: 226 AN: 2112

Alfa AF: 0.0751 Hom.: 2791

Bravo AF: 0.120

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.66
PhyloP100		-0.71
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: rs4742269; hg19: chr9-6849317;