9-7032776-G-A

Variant names:

• chr9-7032776-G-A
• rs1407862
• NM_015061.6:c.2260-14086G>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.2260-14086G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 151,990 control chromosomes in the GnomAD database, including 17,036 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 0.47 (17036 hom., cov: 32)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.58 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	NM_015061.6	MANE Select	c.2260-14086G>A		intron	N/A	NP_055876.2	Q9H3R0-1
	KDM4C	NM_001353997.3		c.2260-14086G>A		intron	N/A	NP_001340926.1
	KDM4C	NM_001304339.4		c.2260-14086G>A		intron	N/A	NP_001291268.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KDM4C	ENST00000381309.8	TSL:1 MANE Select	c.2260-14086G>A		intron	N/A	ENSP00000370710.3	Q9H3R0-1
	KDM4C	ENST00000536108.7	TSL:1	c.2260-14086G>A		intron	N/A	ENSP00000440656.4	Q9H3R0-3
	KDM4C	ENST00000948679.1		c.2260-14086G>A		intron	N/A	ENSP00000618738.1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71511 AN: 151872 Hom.: 17000 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.458

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.471 AC: 71602 AN: 151990 Hom.: 17036 Cov.: 32 AF XY: 0.473 AC XY: 35103 AN XY: 74268

African (AFR) AF: 0.511 AC: 21151 AN: 41422

American (AMR) AF: 0.489 AC: 7483 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1328 AN: 3470

East Asian (EAS) AF: 0.459 AC: 2382 AN: 5184

South Asian (SAS) AF: 0.598 AC: 2880 AN: 4818

European-Finnish (FIN) AF: 0.423 AC: 4466 AN: 10552

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.447 AC: 30403 AN: 67942

Other (OTH) AF: 0.474 AC: 1000 AN: 2110

Alfa AF: 0.463 Hom.: 12302

Bravo AF: 0.472

Asia WGS AF: 0.558 AC: 1938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.23
DANN	Benign	0.21
PhyloP100		-0.24
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: rs1407862; hg19: chr9-7032776;