Variant 7-105062147-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

The NM_182931.3(KMT2E):c.72-17C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00765 in 1,503,746 control chromosomes in the GnomAD database, including 755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.038 ( 407 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 348 hom. )

Consequence

KMT2E
NM_182931.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 7-105062147-C-G is Benign according to our data. Variant chr7-105062147-C-G is described in ClinVar as [Benign]. Clinvar id is 1657509.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMT2E	NM_182931.3 linkuse as main transcript	c.72-17C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000311117.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMT2E	ENST00000311117.8 linkuse as main transcript	c.72-17C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_182931.3	P4	Q8IZD2-1

Frequencies

GnomAD3 genomes

AF:

0.0380

AC:

5778

AN:

151984

Hom.:

402

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000574

Gnomad OTH

AF:

0.0315

GnomAD3 exomes

AF:

0.0100

AC:

2412

AN:

240288

Hom.:

148

AF XY:

0.00750

AC XY:

972

AN XY:

129662

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.00685

Gnomad ASJ exome

AF:

0.000423

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000399

Gnomad FIN exome

AF:

0.0000933

Gnomad NFE exome

AF:

0.000589

Gnomad OTH exome

AF:

0.00582

GnomAD4 exome

AF:

0.00422

AC:

5699

AN:

1351644

Hom.:

348

Cov.:

AF XY:

0.00375

AC XY:

2543

AN XY:

677842

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.00759

Gnomad4 ASJ exome

AF:

0.000200

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000503

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.000312

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.0382

AC:

5810

AN:

152102

Hom.:

407

Cov.:

AF XY:

0.0370

AC XY:

2754

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.0135

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000574

Gnomad4 OTH

AF:

0.0312

Alfa

AF:

0.0195

Hom.:

Bravo

AF:

0.0433

Asia WGS

AF:

0.0110

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

-0.26

CADD

Benign

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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