Variant 11-118519367-A-C 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_001197104.2(KMT2A):c.11147-251A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 420,912 control chromosomes in the GnomAD database, including 2,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1495 hom., cov: 31)

Exomes 𝑓: 0.067 ( 857 hom. )

Consequence

KMT2A
NM_001197104.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.00

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:

TTC36-AS1 (HGNC:55495): (TTC36 and KMT2A antisense RNA 1)

TTC36-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=-0.9).

BP6

Variant 11-118519367-A-C is Benign according to our data. Variant chr11-118519367-A-C is described in ClinVar as [Benign]. Clinvar id is 1179536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 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.11147-251A>C		intron_variant		ENST00000534358.8
TTC36-AS1	NR_120574.1 linkuse as main transcript	n.321+1899T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT2A	ENST00000534358.8 linkuse as main transcript	c.11147-251A>C		intron_variant		1	NM_001197104.2	P4	Q03164-3
TTC36-AS1	ENST00000532597.6 linkuse as main transcript	n.241+1899T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16589

AN:

152074

Hom.:

1488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.241

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0563

Gnomad ASJ

AF:

0.0539

Gnomad EAS

AF:

0.0210

Gnomad SAS

AF:

0.0746

Gnomad FIN

AF:

0.0818

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0599

Gnomad OTH

AF:

0.0808

GnomAD4 exome

AF:

0.0665

AC:

17878

AN:

268720

Hom.:

857

Cov.:

AF XY:

0.0662

AC XY:

9188

AN XY:

138750

show subpopulations

Gnomad4 AFR exome

AF:

0.245

Gnomad4 AMR exome

AF:

0.0447

Gnomad4 ASJ exome

AF:

0.0575

Gnomad4 EAS exome

AF:

0.0306

Gnomad4 SAS exome

AF:

0.0788

Gnomad4 FIN exome

AF:

0.0631

Gnomad4 NFE exome

AF:

0.0608

Gnomad4 OTH exome

AF:

0.0749

GnomAD4 genome

AF:

0.109

AC:

16622

AN:

152192

Hom.:

1495

Cov.:

AF XY:

0.108

AC XY:

8014

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.241

Gnomad4 AMR

AF:

0.0562

Gnomad4 ASJ

AF:

0.0539

Gnomad4 EAS

AF:

0.0212

Gnomad4 SAS

AF:

0.0748

Gnomad4 FIN

AF:

0.0818

Gnomad4 NFE

AF:

0.0599

Gnomad4 OTH

AF:

0.0799

Alfa

AF:

0.0783

Hom.:

139

Bravo

AF:

0.114

Asia WGS

AF:

0.0550

AC:

192

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	clinical testing	GeneDx	Aug 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.15

DANN

Benign

0.70

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