NM_014663.3:c.623+1021A>G

Variant names:

• chr1-43664108-A-G
• rs669446
• NM_014663.3:c.623+1021A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014663.3(KDM4A):​c.623+1021A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.739 in 152,126 control chromosomes in the GnomAD database, including 42,644 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 0.74 (42644 hom., cov: 31)
• Consequence: KDM4A NM_014663.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 15 publications found

Genes affected

KDM4A (HGNC:22978): (lysine demethylase 4A) This gene is a member of the Jumonji domain 2 (JMJD2) family and encodes a protein containing a JmjN domain, a JmjC domain, a JD2H domain, two TUDOR domains, and two PHD-type zinc fingers. This nuclear protein functions as a trimethylation-specific demethylase, converting specific trimethylated histone residues to the dimethylated form, and as a transcriptional repressor. [provided by RefSeq, Apr 2009]

ENSG00000284989 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KDM4A	NM_014663.3	c.623+1021A>G		intron_variant	Intron 5 of 21	ENST00000372396.4	NP_055478.2
LOC124904165	XR_007066050.1	n.1228T>C		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KDM4A	ENST00000372396.4	c.623+1021A>G		intron_variant	Intron 5 of 21	1	NM_014663.3	ENSP00000361473.3
ENSG00000284989	ENST00000645057.1	n.623+1021A>G		intron_variant	Intron 5 of 25			ENSP00000494063.1
KDM4A	ENST00000463151.5	c.623+1021A>G		intron_variant	Intron 5 of 7	5		ENSP00000493741.1
KDM4A	ENST00000485249.1	n.*604+1021A>G		intron_variant	Intron 5 of 7	3		ENSP00000496362.1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112308 AN: 152008 Hom.: 42591 Cov.: 31

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.739 AC: 112419 AN: 152126 Hom.: 42644 Cov.: 31 AF XY: 0.733 AC XY: 54497 AN XY: 74358

African (AFR) AF: 0.908 AC: 37695 AN: 41532

American (AMR) AF: 0.580 AC: 8858 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2245 AN: 3466

East Asian (EAS) AF: 0.821 AC: 4247 AN: 5172

South Asian (SAS) AF: 0.594 AC: 2861 AN: 4818

European-Finnish (FIN) AF: 0.690 AC: 7292 AN: 10574

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46837 AN: 67972

Other (OTH) AF: 0.705 AC: 1489 AN: 2112

Alfa AF: 0.706 Hom.: 86727

Bravo AF: 0.740

Asia WGS AF: 0.721 AC: 2507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.57
PhyloP100		0.13
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: rs669446; hg19: chr1-44129779; COSMIC: COSV64959110; COSMIC: COSV64959110;