Variant chr11-118484927-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001197104.2(KMT2A):c.4284A>C(p.Ile1428=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0571 in 1,613,484 control chromosomes in the GnomAD database, including 2,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 185 hom., cov: 32)

Exomes 𝑓: 0.059 ( 2788 hom. )

Consequence

KMT2A
NM_001197104.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.77

Variant links:

Genes affected

KMT2A (HGNC:7132): (lysine methyltransferase 2A) This gene encodes a transcriptional coactivator that plays an essential role in regulating gene expression during early development and hematopoiesis. The encoded protein contains multiple conserved functional domains. One of these domains, the SET domain, is responsible for its histone H3 lysine 4 (H3K4) methyltransferase activity which mediates chromatin modifications associated with epigenetic transcriptional activation. This protein is processed by the enzyme Taspase 1 into two fragments, MLL-C and MLL-N. These fragments reassociate and further assemble into different multiprotein complexes that regulate the transcription of specific target genes, including many of the HOX genes. Multiple chromosomal translocations involving this gene are the cause of certain acute lymphoid leukemias and acute myeloid leukemias. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]

KMT2A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 11-118484927-A-C is Benign according to our data. Variant chr11-118484927-A-C is described in ClinVar as [Benign]. Clinvar id is 158702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-118484927-A-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.77 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT2A	NM_001197104.2 linkuse as main transcript	c.4284A>C	p.Ile1428=	synonymous_variant	10/36	ENST00000534358.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT2A	ENST00000534358.8 linkuse as main transcript	c.4284A>C	p.Ile1428=	synonymous_variant	10/36	1	NM_001197104.2	P4	Q03164-3

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6321

AN:

152174

Hom.:

185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0101

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0255

Gnomad ASJ

AF:

0.0472

Gnomad EAS

AF:

0.0310

Gnomad SAS

AF:

0.0678

Gnomad FIN

AF:

0.0817

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0574

Gnomad OTH

AF:

0.0353

GnomAD3 exomes

AF:

0.0500

AC:

12569

AN:

251238

Hom.:

401

AF XY:

0.0532

AC XY:

7230

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.00953

Gnomad AMR exome

AF:

0.0218

Gnomad ASJ exome

AF:

0.0526

Gnomad EAS exome

AF:

0.0234

Gnomad SAS exome

AF:

0.0754

Gnomad FIN exome

AF:

0.0702

Gnomad NFE exome

AF:

0.0577

Gnomad OTH exome

AF:

0.0514

GnomAD4 exome

AF:

0.0588

AC:

85866

AN:

1461192

Hom.:

2788

Cov.:

AF XY:

0.0598

AC XY:

43453

AN XY:

726904

show subpopulations

Gnomad4 AFR exome

AF:

0.00863

Gnomad4 AMR exome

AF:

0.0229

Gnomad4 ASJ exome

AF:

0.0541

Gnomad4 EAS exome

AF:

0.0469

Gnomad4 SAS exome

AF:

0.0763

Gnomad4 FIN exome

AF:

0.0654

Gnomad4 NFE exome

AF:

0.0608

Gnomad4 OTH exome

AF:

0.0550

GnomAD4 genome

AF:

0.0415

AC:

6321

AN:

152292

Hom.:

185

Cov.:

AF XY:

0.0426

AC XY:

3169

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.0254

Gnomad4 ASJ

AF:

0.0472

Gnomad4 EAS

AF:

0.0312

Gnomad4 SAS

AF:

0.0683

Gnomad4 FIN

AF:

0.0817

Gnomad4 NFE

AF:

0.0574

Gnomad4 OTH

AF:

0.0350

Alfa

AF:

0.0538

Hom.:

243

Bravo

AF:

0.0363

Asia WGS

AF:

0.0430

AC:

150

AN:

3478

EpiCase

AF:

0.0559

EpiControl

AF:

0.0570

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 19, 2013	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.5

DANN

Benign

0.78

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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