Variant chr1-43703746-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014663.3(KDM4A):c.2961+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 1,613,914 control chromosomes in the GnomAD database, including 281 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 137 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 144 hom. )

Consequence

KDM4A
NM_014663.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.193

Variant links:

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]

KDM4A links:

KDM4A-AS1 (HGNC:):

KDM4A-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 1-43703746-G-A is Benign according to our data. Variant chr1-43703746-G-A is described in ClinVar as [Benign]. Clinvar id is 775543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KDM4A	NM_014663.3 linkuse as main transcript	c.2961+10G>A		intron_variant		ENST00000372396.4	NP_055478.2	O75164-1
KDM4A-AS1	NR_033827.1 linkuse as main transcript	n.389-99C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KDM4A	ENST00000372396.4 linkuse as main transcript	c.2961+10G>A		intron_variant		1	NM_014663.3	ENSP00000361473.3		O75164-1
ENSG00000284989	ENST00000645057.1 linkuse as main transcript	n.*1199+10G>A		intron_variant				ENSP00000494063.1		A0A2R8Y4U1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3399

AN:

152146

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0783

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00681

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00590

AC:

1482

AN:

251220

Hom.:

AF XY:

0.00445

AC XY:

604

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.0808

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000238

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00244

AC:

3565

AN:

1461650

Hom.:

144

Cov.:

AF XY:

0.00208

AC XY:

1512

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.0869

Gnomad4 AMR exome

AF:

0.00398

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000791

Gnomad4 OTH exome

AF:

0.00565

GnomAD4 genome

AF:

0.0225

AC:

3420

AN:

152264

Hom.:

137

Cov.:

AF XY:

0.0218

AC XY:

1625

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0786

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0181

Hom.:

Bravo

AF:

0.0266

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 02, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.5

DANN

Benign

0.61

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over