dbSNP rs3829382: FLT3:c.*501C>A (chr13-28003551-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004119.3(FLT3):c.*501C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 236,966 control chromosomes in the GnomAD database, including 27,140 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 16557 hom., cov: 32)

Exomes 𝑓: 0.50 ( 10583 hom. )

Consequence

FLT3
NM_004119.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.79

Publications

17 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT3	NM_004119.3 link	c.*501C>A		3_prime_UTR_variant	Exon 24 of 24	ENST00000241453.12	NP_004110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT3	ENST00000241453.12 link	c.*501C>A		3_prime_UTR_variant	Exon 24 of 24	1	NM_004119.3	ENSP00000241453.7
FLT3	ENST00000380987.2 link	n.*1395C>A		downstream_gene_variant		1		ENSP00000370374.2

Frequencies

GnomAD3 genomes

AF:

0.460

AC:

69821

AN:

151824

Hom.:

16548

Cov.:

show subpopulations

Gnomad AFR

AF:

0.369

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.500

Gnomad EAS

AF:

0.502

Gnomad SAS

AF:

0.631

Gnomad FIN

AF:

0.436

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.483

GnomAD4 exome

AF:

0.497

AC:

42286

AN:

85024

Hom.:

10583

Cov.:

AF XY:

0.497

AC XY:

19601

AN XY:

39422

show subpopulations

African (AFR)

AF:

0.374

AC:

1465

AN:

3920

American (AMR)

AF:

0.431

AC:

1452

AN:

3370

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

2530

AN:

5156

East Asian (EAS)

AF:

0.550

AC:

6407

AN:

11654

South Asian (SAS)

AF:

0.598

AC:

614

AN:

1026

European-Finnish (FIN)

AF:

0.455

AC:

225

AN:

494

Middle Eastern (MID)

AF:

0.437

AC:

215

AN:

492

European-Non Finnish (NFE)

AF:

0.500

AC:

26013

AN:

52044

Other (OTH)

AF:

0.490

AC:

3365

AN:

6868

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1102

2204

3305

4407

5509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.460

AC:

69858

AN:

151942

Hom.:

16557

Cov.:

AF XY:

0.460

AC XY:

34166

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.368

AC:

15256

AN:

41432

American (AMR)

AF:

0.453

AC:

6905

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

1735

AN:

3470

East Asian (EAS)

AF:

0.503

AC:

2594

AN:

5156

South Asian (SAS)

AF:

0.631

AC:

3030

AN:

4802

European-Finnish (FIN)

AF:

0.436

AC:

4607

AN:

10570

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.503

AC:

34164

AN:

67954

Other (OTH)

AF:

0.486

AC:

1021

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1876

3751

5627

7502

9378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.496

Hom.:

77594

Bravo

AF:

0.457

Asia WGS

AF:

0.554

AC:

1925

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.1

(source)

DANN

Benign

0.58

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over