rs7948661

Positions:

• chr11-118470934-T-C

Variant summary

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

The ENST00000534358.8(KMT2A):​c.503-728T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0615 in 152,262 control chromosomes in the GnomAD database, including 330 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 0.061 (330 hom., cov: 33)
• Consequence: KMT2A ENST00000534358.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752

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=-0.89).
• 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
KMT2A	NM_001197104.2	c.503-728T>C		intron_variant		ENST00000534358.8	NP_001184033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KMT2A	ENST00000534358.8	c.503-728T>C		intron_variant		1	NM_001197104.2	ENSP00000436786	P4

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9343 AN: 152146 Hom.: 330 Cov.: 33

Gnomad AFR AF: 0.0784

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0364

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.0663

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0573

Gnomad OTH AF: 0.0511

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

GnomAD4 genome AF: 0.0615 AC: 9360 AN: 152262 Hom.: 330 Cov.: 33 AF XY: 0.0620 AC XY: 4615 AN XY: 74446

Gnomad4 AFR AF: 0.0786

Gnomad4 AMR AF: 0.0364

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.0318

Gnomad4 SAS AF: 0.0667

Gnomad4 FIN AF: 0.0815

Gnomad4 NFE AF: 0.0573

Gnomad4 OTH AF: 0.0506

Alfa AF: 0.0574 Hom.: 36

Bravo AF: 0.0598

Asia WGS AF: 0.0470 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.041
DANN	Benign	0.62

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: rs7948661; hg19: chr11-118341649;