Variant 13-28015358-C-G 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.2654-102G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 857,866 control chromosomes in the GnomAD database, including 61,629 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8728 hom., cov: 30)

Exomes 𝑓: 0.37 ( 52901 hom. )

Consequence

FLT3
NM_004119.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.612

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:

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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=-0.82).

BP6

Variant 13-28015358-C-G is Benign according to our data. Variant chr13-28015358-C-G is described in ClinVar as [Benign]. Clinvar id is 1283726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 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.2654-102G>C		intron_variant		ENST00000241453.12	NP_004110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT3	ENST00000241453.12 linkuse as main transcript	c.2654-102G>C		intron_variant		1	NM_004119.3	ENSP00000241453	P1	P36888-1
FLT3	ENST00000380987.2 linkuse as main transcript	c.*566-102G>C		intron_variant, NMD_transcript_variant		1		ENSP00000370374

Frequencies

GnomAD3 genomes

AF:

0.316

AC:

47995

AN:

151836

Hom.:

8725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.433

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.430

Gnomad OTH

AF:

0.368

GnomAD4 exome

AF:

0.373

AC:

263296

AN:

705910

Hom.:

52901

AF XY:

0.369

AC XY:

137894

AN XY:

373240

show subpopulations

Gnomad4 AFR exome

AF:

0.152

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.440

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.243

Gnomad4 FIN exome

AF:

0.317

Gnomad4 NFE exome

AF:

0.429

Gnomad4 OTH exome

AF:

0.369

GnomAD4 genome

AF:

0.316

AC:

47989

AN:

151956

Hom.:

8728

Cov.:

AF XY:

0.307

AC XY:

22776

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.290

Gnomad4 ASJ

AF:

0.433

Gnomad4 EAS

AF:

0.161

Gnomad4 SAS

AF:

0.228

Gnomad4 FIN

AF:

0.304

Gnomad4 NFE

AF:

0.430

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.370

Hom.:

1391

Bravo

AF:

0.306

Asia WGS

AF:

0.193

AC:

672

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	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.3

DANN

Benign

0.46

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