Variant chr13-28015231-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_004119.3(FLT3):c.2679G>A(p.Pro893=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000447 in 1,611,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

FLT3
NM_004119.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.40

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 13-28015231-C-T is Benign according to our data. Variant chr13-28015231-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 731549.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.4 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000743 (113/152140) while in subpopulation AFR AF= 0.00193 (80/41500). AF 95% confidence interval is 0.00159. There are 0 homozygotes in gnomad4. There are 60 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT3	NM_004119.3 linkuse as main transcript	c.2679G>A	p.Pro893=	synonymous_variant	22/24	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.2679G>A	p.Pro893=	synonymous_variant	22/24	1	NM_004119.3	ENSP00000241453	P1	P36888-1
FLT3	ENST00000380987.2 linkuse as main transcript	c.*591G>A		3_prime_UTR_variant, NMD_transcript_variant	23/25	1		ENSP00000370374

Frequencies

GnomAD3 genomes

AF:

0.000743

AC:

113

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.000371

AC:

AN:

250586

Hom.:

AF XY:

0.000332

AC XY:

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.00179

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000521

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000417

AC:

608

AN:

1459074

Hom.:

Cov.:

AF XY:

0.000438

AC XY:

318

AN XY:

725982

show subpopulations

Gnomad4 AFR exome

AF:

0.00192

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000465

Gnomad4 FIN exome

AF:

0.000281

Gnomad4 NFE exome

AF:

0.000423

Gnomad4 OTH exome

AF:

0.000779

GnomAD4 genome

AF:

0.000743

AC:

113

AN:

152140

Hom.:

Cov.:

AF XY:

0.000806

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00193

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.000577

Hom.:

Bravo

AF:

0.000771

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000475

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.7

DANN

Benign

0.41

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