rs7019027

Positions:

• chr9-7051826-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015061.6(KDM4C):​c.2424+2626G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,150 control chromosomes in the GnomAD database, including 2,522 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 0.16 (2522 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM4C	NM_015061.6	c.2424+2626G>A		intron_variant		ENST00000381309.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM4C	ENST00000381309.8	c.2424+2626G>A		intron_variant		1	NM_015061.6	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23796 AN: 152032 Hom.: 2518 Cov.: 32

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.157 AC: 23814 AN: 152150 Hom.: 2522 Cov.: 32 AF XY: 0.162 AC XY: 12021 AN XY: 74378

Gnomad4 AFR AF: 0.0557

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.159

Alfa AF: 0.176 Hom.: 4257

Bravo AF: 0.159

Asia WGS AF: 0.314 AC: 1088 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	0.24
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs7019027; hg19: chr9-7051826;