rs7040123

Variant names:

• chr9-7170742-A-G
• rs7040123
• NM_015061.6:c.2994+852A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-7170742-A-G
• chr9-7170742-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.89).
• 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 rank	MANE	Protein	UniProt
KDM4C	NM_015061.6	c.2994+852A>G		intron_variant	Intron 21 of 21	ENST00000381309.8	NP_055876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4C	ENST00000381309.8	c.2994+852A>G		intron_variant	Intron 21 of 21	1	NM_015061.6	ENSP00000370710.3
KDM4C	ENST00000381306.7	c.*702A>G		3_prime_UTR_variant	Exon 21 of 21	2		ENSP00000370707.3
KDM4C	ENST00000428870.6	c.2055+852A>G		intron_variant	Intron 14 of 14	2		ENSP00000405739.2

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

African (AFR) AF: 0.105 AC: 1646 AN: 15706

American (AMR) AF: 0.0265 AC: 26 AN: 980

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 285 AN: 5126

East Asian (EAS) AF: 0.0377 AC: 136 AN: 3612

South Asian (SAS) AF: 0.0978 AC: 1601 AN: 16368

European-Finnish (FIN) AF: 0.0365 AC: 10 AN: 274

Middle Eastern (MID) AF: 0.0829 AC: 134 AN: 1616

European-Non Finnish (NFE) AF: 0.0325 AC: 24693 AN: 759188

Other (OTH) AF: 0.0452 AC: 1229 AN: 27176

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

African (AFR) AF: 0.100 AC: 4161 AN: 41442

American (AMR) AF: 0.0399 AC: 610 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0510 AC: 177 AN: 3472

East Asian (EAS) AF: 0.0458 AC: 237 AN: 5180

South Asian (SAS) AF: 0.0927 AC: 447 AN: 4824

European-Finnish (FIN) AF: 0.0511 AC: 540 AN: 10566

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0338 AC: 2300 AN: 68010

Other (OTH) AF: 0.0615 AC: 130 AN: 2114

Alfa AF: 0.0393 Hom.: 234

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
PhyloP100		-0.039
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: rs7040123; hg19: chr9-7170742;