rs7040123

chr9-7170742-A-Gchr9-7170742-A-T

Variant summary

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

The NM_015061.6(KDM4C):c.2994+852A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0392 in 982,140 control chromosomes in the GnomAD database, including 956 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 0.057 (323 hom., cov: 32)
  • Exomes 𝑓: 0.036 (633 hom.)
• Consequence: KDM4C NM_015061.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM4C	NM_015061.6	c.2994+852A>G		intron_variant		ENST00000381309.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM4C	ENST00000381309.8	c.2994+852A>G		intron_variant		1	NM_015061.6	P1
KDM4C	ENST00000381306.7	c.*702A>G		3_prime_UTR_variant	21/21	2
KDM4C	ENST00000428870.6	c.2055+852A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0571 AC: 8675 AN: 151976 Hom.: 320 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.0400

Gnomad ASJ AF: 0.0510

Gnomad EAS AF: 0.0455

Gnomad SAS AF: 0.0930

Gnomad FIN AF: 0.0511

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0338

Gnomad OTH AF: 0.0617

GnomAD4 exome AF: 0.0359 AC: 29760 AN: 830046 Hom.: 633 Cov.: 19 AF XY: 0.0360 AC XY: 13802 AN XY: 383416

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.0265

Gnomad4 ASJ exome AF: 0.0556

Gnomad4 EAS exome AF: 0.0377

Gnomad4 SAS exome AF: 0.0978

Gnomad4 FIN exome AF: 0.0365

Gnomad4 NFE exome AF: 0.0325

Gnomad4 OTH exome AF: 0.0452

GnomAD4 genome AF: 0.0572 AC: 8699 AN: 152094 Hom.: 323 Cov.: 32 AF XY: 0.0581 AC XY: 4321 AN XY: 74350

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.0399

Gnomad4 ASJ AF: 0.0510

Gnomad4 EAS AF: 0.0458

Gnomad4 SAS AF: 0.0927

Gnomad4 FIN AF: 0.0511

Gnomad4 NFE AF: 0.0338

Gnomad4 OTH AF: 0.0615

Alfa AF: 0.0371 Hom.: 141

Bravo AF: 0.0570

Asia WGS AF: 0.0750 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.75
Dann	Benign	0.52

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: rs7040123; hg19: chr9-7170742;