Variant 13-28015130-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004119.3(FLT3):c.2753+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,419,534 control chromosomes in the GnomAD database, including 175,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16540 hom., cov: 32)

Exomes 𝑓: 0.50 ( 158952 hom. )

Consequence

FLT3
NM_004119.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.272

Variant links:

Genes affected

FLT3 (HGNC:3765): (fms related receptor tyrosine kinase 3) This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. [provided by RefSeq, Jan 2015]

FLT3 links:

FLT3 (HGNC:):

FLT3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 13-28015130-C-T is Benign according to our data. Variant chr13-28015130-C-T is described in ClinVar as [Benign]. Clinvar id is 1243109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT3	NM_004119.3 linkuse as main transcript	c.2753+27G>A		intron_variant		ENST00000241453.12	NP_004110.2	P36888-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT3	ENST00000241453.12 linkuse as main transcript	c.2753+27G>A		intron_variant		1	NM_004119.3	ENSP00000241453.7		P36888-1
FLT3	ENST00000380987.2 linkuse as main transcript	n.*665+27G>A		intron_variant		1		ENSP00000370374.2		E7ER61

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68393

AN:

151814

Hom.:

16540

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.501

Gnomad ASJ

AF:

0.485

Gnomad EAS

AF:

0.413

Gnomad SAS

AF:

0.312

Gnomad FIN

AF:

0.604

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.523

Gnomad OTH

AF:

0.440

GnomAD3 exomes

AF:

0.477

AC:

108782

AN:

228208

Hom.:

26752

AF XY:

0.472

AC XY:

58172

AN XY:

123192

show subpopulations

Gnomad AFR exome

AF:

0.290

Gnomad AMR exome

AF:

0.524

Gnomad ASJ exome

AF:

0.493

Gnomad EAS exome

AF:

0.407

Gnomad SAS exome

AF:

0.328

Gnomad FIN exome

AF:

0.595

Gnomad NFE exome

AF:

0.517

Gnomad OTH exome

AF:

0.478

GnomAD4 exome

AF:

0.496

AC:

628549

AN:

1267602

Hom.:

158952

Cov.:

AF XY:

0.491

AC XY:

314010

AN XY:

639024

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.523

Gnomad4 ASJ exome

AF:

0.489

Gnomad4 EAS exome

AF:

0.400

Gnomad4 SAS exome

AF:

0.332

Gnomad4 FIN exome

AF:

0.588

Gnomad4 NFE exome

AF:

0.516

Gnomad4 OTH exome

AF:

0.475

GnomAD4 genome

AF:

0.450

AC:

68416

AN:

151932

Hom.:

16540

Cov.:

AF XY:

0.454

AC XY:

33679

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.290

Gnomad4 AMR

AF:

0.501

Gnomad4 ASJ

AF:

0.485

Gnomad4 EAS

AF:

0.412

Gnomad4 SAS

AF:

0.312

Gnomad4 FIN

AF:

0.604

Gnomad4 NFE

AF:

0.523

Gnomad4 OTH

AF:

0.437

Alfa

AF:

0.484

Hom.:

3827

Bravo

AF:

0.436

Asia WGS

AF:

0.340

AC:

1183

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.9

DANN

Benign

0.79

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