rs34172843

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004119.3(FLT3):c.1073A>T(p.Asp358Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000626 in 1,610,464 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00083 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 10 hom. )

Consequence

FLT3
NM_004119.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 2.52

Publications

14 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009637773).

BP6

Variant 13-28048407-T-A is Benign according to our data. Variant chr13-28048407-T-A is described in ClinVar as [Benign]. Clinvar id is 134452.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000827 (126/152342) while in subpopulation EAS AF = 0.021 (109/5186). AF 95% confidence interval is 0.0178. There are 2 homozygotes in GnomAd4. There are 74 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 126 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT3	NM_004119.3 link	c.1073A>T	p.Asp358Val	missense_variant	Exon 9 of 24	ENST00000241453.12	NP_004110.2	P36888-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT3	ENST00000241453.12 link	c.1073A>T	p.Asp358Val	missense_variant	Exon 9 of 24	1	NM_004119.3	ENSP00000241453.7		P36888-1
FLT3	ENST00000380987.2 link	n.1073A>T		non_coding_transcript_exon_variant	Exon 9 of 25	1		ENSP00000370374.2		E7ER61

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.0210

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00192

AC:

482

AN:

250702

AF XY:

0.00168

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00358

Gnomad EAS exome

AF:

0.0236

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000605

AC:

882

AN:

1458122

Hom.:

Cov.:

AF XY:

0.000584

AC XY:

424

AN XY:

725644

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33414

American (AMR)

AF:

0.00

AC:

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.00398

AC:

104

AN:

26108

East Asian (EAS)

AF:

0.0168

AC:

665

AN:

39660

South Asian (SAS)

AF:

0.000290

AC:

AN:

86064

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000307

AC:

AN:

1108784

Other (OTH)

AF:

0.000880

AC:

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

131

174

218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000827

AC:

126

AN:

152342

Hom.:

Cov.:

AF XY:

0.000993

AC XY:

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41586

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3472

East Asian (EAS)

AF:

0.0210

AC:

109

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000709

Hom.:

Bravo

AF:

0.00125

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00180

AC:

218

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Benign

-0.014

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0096

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.6

PhyloP100

2.5

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.33

Sift

Benign

0.066

Sift4G

Benign

0.13

Polyphen

0.45

Vest4

0.34

MVP

0.76

MPC

0.25

ClinPred

0.036

GERP RS

5.5

Varity_R

0.34

gMVP

0.67

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs34172843

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over