rs613976

Positions:

• chr1-43654326-T-A
• chr1-43654326-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_014663.3(KDM4A):​c.138+1013T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,138 control chromosomes in the GnomAD database, including 15,794 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 0.45 (15794 hom., cov: 33)
• Consequence: KDM4A NM_014663.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.994

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM4A	NM_014663.3	c.138+1013T>A		intron_variant		ENST00000372396.4	NP_055478.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM4A	ENST00000372396.4	c.138+1013T>A		intron_variant		1	NM_014663.3	ENSP00000361473.3
ENSG00000284989	ENST00000645057.1	n.138+1013T>A		intron_variant				ENSP00000494063.1
KDM4A	ENST00000463151.5	c.138+1013T>A		intron_variant		5		ENSP00000493741.1
KDM4A	ENST00000485249.1	n.*119+527T>A		intron_variant		3		ENSP00000496362.1

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68657 AN: 152020 Hom.: 15770 Cov.: 33

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.452 AC: 68726 AN: 152138 Hom.: 15794 Cov.: 33 AF XY: 0.447 AC XY: 33242 AN XY: 74388

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.469

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.484

Alfa AF: 0.452 Hom.: 1994

Bravo AF: 0.450

Asia WGS AF: 0.295 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	18
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.31		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs613976; hg19: chr1-44119997;