chr1-43651335-G-T

Position:

• chr1-43651335-G-T

Variant summary

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

The NM_014663.3(KDM4A):​c.-40+1083G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,136 control chromosomes in the GnomAD database, including 6,750 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 0.29 (6750 hom., cov: 33)
• Consequence: KDM4A NM_014663.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.903

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KDM4A	NM_014663.3	c.-40+1083G>T		intron_variant		ENST00000372396.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KDM4A	ENST00000372396.4	c.-40+1083G>T		intron_variant		1	NM_014663.3	P1
KDM4A	ENST00000463151.5	c.-40+661G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43960 AN: 152018 Hom.: 6746 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.289 AC: 43981 AN: 152136 Hom.: 6750 Cov.: 33 AF XY: 0.285 AC XY: 21208 AN XY: 74368

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.330

Alfa AF: 0.332 Hom.: 7456

Bravo AF: 0.282

Asia WGS AF: 0.174 AC: 607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.51

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: rs660899; hg19: chr1-44117006;