Variant rs11168830 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003482.4(KMT2D):c.13689C>T(p.Pro4563Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0573 in 1,613,506 control chromosomes in the GnomAD database, including 5,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 684 hom., cov: 32)

Exomes 𝑓: 0.056 ( 5197 hom. )

Consequence

KMT2D
NM_003482.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.30

Variant links:

Genes affected

KMT2D (HGNC:7133): (lysine methyltransferase 2D) The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]

KMT2D links:

KMT2D (HGNC:):

KMT2D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 12-49030751-G-A is Benign according to our data. Variant chr12-49030751-G-A is described in ClinVar as [Benign]. Clinvar id is 94169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-49030751-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMT2D	NM_003482.4 linkuse as main transcript	c.13689C>T	p.Pro4563Pro	synonymous_variant	42/55	ENST00000301067.12	NP_003473.3	O14686-1Q59FG6Q6PIA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KMT2D	ENST00000301067.12 linkuse as main transcript	c.13689C>T	p.Pro4563Pro	synonymous_variant	42/55	5	NM_003482.4	ENSP00000301067.7		O14686-1

Frequencies

GnomAD3 genomes

AF:

0.0672

AC:

10225

AN:

152110

Hom.:

679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0525

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.0464

Gnomad EAS

AF:

0.264

Gnomad SAS

AF:

0.0977

Gnomad FIN

AF:

0.0607

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0346

Gnomad OTH

AF:

0.0664

GnomAD3 exomes

AF:

0.103

AC:

25558

AN:

248488

Hom.:

2932

AF XY:

0.0914

AC XY:

12339

AN XY:

135018

show subpopulations

Gnomad AFR exome

AF:

0.0531

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.0430

Gnomad EAS exome

AF:

0.255

Gnomad SAS exome

AF:

0.0854

Gnomad FIN exome

AF:

0.0634

Gnomad NFE exome

AF:

0.0361

Gnomad OTH exome

AF:

0.0766

GnomAD4 exome

AF:

0.0562

AC:

82166

AN:

1461278

Hom.:

5197

Cov.:

AF XY:

0.0555

AC XY:

40313

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.0519

Gnomad4 AMR exome

AF:

0.307

Gnomad4 ASJ exome

AF:

0.0434

Gnomad4 EAS exome

AF:

0.255

Gnomad4 SAS exome

AF:

0.0847

Gnomad4 FIN exome

AF:

0.0631

Gnomad4 NFE exome

AF:

0.0366

Gnomad4 OTH exome

AF:

0.0640

GnomAD4 genome

AF:

0.0673

AC:

10249

AN:

152228

Hom.:

684

Cov.:

AF XY:

0.0706

AC XY:

5253

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0525

Gnomad4 AMR

AF:

0.188

Gnomad4 ASJ

AF:

0.0464

Gnomad4 EAS

AF:

0.264

Gnomad4 SAS

AF:

0.0976

Gnomad4 FIN

AF:

0.0607

Gnomad4 NFE

AF:

0.0346

Gnomad4 OTH

AF:

0.0733

Alfa

AF:

0.0406

Hom.:

306

Bravo

AF:

0.0810

Asia WGS

AF:

0.186

AC:

646

AN:

3478

EpiCase

AF:

0.0340

EpiControl

AF:

0.0347

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 23, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 42% of patients studied by a panel of primary immunodeficiencies. Number of patients: 40. Only high quality variants are reported. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Kabuki syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.2

DANN

Benign

0.50

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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