chr9-7030268-G-T

Position:

• chr9-7030268-G-T

Variant summary

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

The NM_015061.6(KDM4C):​c.2259+14339G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,932 control chromosomes in the GnomAD database, including 14,807 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 0.44 (14807 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM4C	NM_015061.6	c.2259+14339G>T		intron_variant		ENST00000381309.8	NP_055876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8	c.2259+14339G>T		intron_variant		1	NM_015061.6	ENSP00000370710	P1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66537 AN: 151814 Hom.: 14785 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.438 AC: 66612 AN: 151932 Hom.: 14807 Cov.: 32 AF XY: 0.441 AC XY: 32768 AN XY: 74272

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.444

Alfa AF: 0.439 Hom.: 28092

Bravo AF: 0.434

Asia WGS AF: 0.543 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.42

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: rs10758821; hg19: chr9-7030268;