7-104952120-T-C

Variant names:

• chr7-104952120-T-C
• rs2428161
• ENST00000622386.2:c.-467-9864T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000415513.1(KMT2E):​n.609-9864T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,002 control chromosomes in the GnomAD database, including 16,950 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 0.47 (16950 hom., cov: 32)
• Consequence: KMT2E ENST00000415513.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 6 publications found

Genes affected

KMT2E (HGNC:18541): (lysine methyltransferase 2E (inactive)) This gene is a member of the myeloid/lymphoid or mixed-lineage leukemia (MLL) family and encodes a protein with an N-terminal PHD zinc finger and a central SET domain. Overexpression of the protein inhibits cell cycle progression. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]

KMT2E-AS1 (HGNC:40845): (KMT2E antisense RNA 1)

LOC101927902 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000415513.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC101927902	NR_187678.1		n.803-9864T>C		intron	N/A
	LOC101927902	NR_187679.1		n.728-9864T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KMT2E	ENST00000622386.2	TSL:5	c.-467-9864T>C		intron	N/A	ENSP00000482147.2	A0A087WYW5
	KMT2E	ENST00000415513.1	TSL:2	n.609-9864T>C		intron	N/A
	KMT2E-AS1	ENST00000450686.2	TSL:3	n.334+1580A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71335 AN: 151882 Hom.: 16927 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.470 AC: 71398 AN: 152002 Hom.: 16950 Cov.: 32 AF XY: 0.468 AC XY: 34784 AN XY: 74296

African (AFR) AF: 0.513 AC: 21253 AN: 41430

American (AMR) AF: 0.483 AC: 7385 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1542 AN: 3466

East Asian (EAS) AF: 0.477 AC: 2466 AN: 5166

South Asian (SAS) AF: 0.366 AC: 1762 AN: 4814

European-Finnish (FIN) AF: 0.442 AC: 4673 AN: 10566

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30701 AN: 67954

Other (OTH) AF: 0.474 AC: 1001 AN: 2114

Alfa AF: 0.454 Hom.: 15206

Bravo AF: 0.479

Asia WGS AF: 0.421 AC: 1467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.1
DANN	Benign	0.52
PhyloP100		-0.23

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2428161; hg19: chr7-104592567;