rs2017122

Positions:

• chr11-118444134-C-T

Variant summary

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

The NM_001197104.2(KMT2A):​c.432+7190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0413 in 152,210 control chromosomes in the GnomAD database, including 185 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 0.041 (185 hom., cov: 32)
• Consequence: KMT2A NM_001197104.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMT2A	NM_001197104.2	c.432+7190C>T		intron_variant		ENST00000534358.8	NP_001184033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KMT2A	ENST00000534358.8	c.432+7190C>T		intron_variant		1	NM_001197104.2	ENSP00000436786	P4

Frequencies

GnomAD3 genomes AF: 0.0413 AC: 6285 AN: 152092 Hom.: 185 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0252

Gnomad ASJ AF: 0.0472

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.0667

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.0349

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

GnomAD4 genome AF: 0.0413 AC: 6285 AN: 152210 Hom.: 185 Cov.: 32 AF XY: 0.0424 AC XY: 3155 AN XY: 74432

Gnomad4 AFR AF: 0.00999

Gnomad4 AMR AF: 0.0251

Gnomad4 ASJ AF: 0.0472

Gnomad4 EAS AF: 0.0326

Gnomad4 SAS AF: 0.0671

Gnomad4 FIN AF: 0.0812

Gnomad4 NFE AF: 0.0571

Gnomad4 OTH AF: 0.0346

Alfa AF: 0.0496 Hom.: 45

Bravo AF: 0.0360

Asia WGS AF: 0.0420 AC: 146 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.23

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: rs2017122; hg19: chr11-118314849; COSMIC: COSV63286313;