rs3736061

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182925.5(FLT4):c.507G>T(p.Leu169Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0791 in 1,612,042 control chromosomes in the GnomAD database, including 5,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 475 hom., cov: 32)

Exomes 𝑓: 0.080 ( 5184 hom. )

Consequence

FLT4
NM_182925.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.144

Publications

22 publications found

Variant links:

Genes affected

FLT4 (HGNC:3767): (fms related receptor tyrosine kinase 4) This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA. [provided by RefSeq, Jul 2008]

FLT4 Gene-Disease associations (from GenCC):

lymphatic malformation 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
capillary infantile hemangioma
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
congenital heart defects, multiple types, 7
Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
lymphatic malformation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
tetralogy of fallot
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FLT4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 5-180630231-C-A is Benign according to our data. Variant chr5-180630231-C-A is described in ClinVar as Benign. ClinVar VariationId is 263064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.144 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.507G>T	p.Leu169Leu	synonymous_variant	Exon 4 of 30	ENST00000261937.11	NP_891555.2	P35916-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11 link	c.507G>T	p.Leu169Leu	synonymous_variant	Exon 4 of 30	1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.0670

AC:

10183

AN:

152082

Hom.:

475

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0465

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.0590

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0867

Gnomad OTH

AF:

0.0535

GnomAD2 exomes

AF:

0.0766

AC:

19113

AN:

249510

AF XY:

0.0775

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.0313

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.0800

Gnomad OTH exome

AF:

0.0760

GnomAD4 exome

AF:

0.0803

AC:

117259

AN:

1459842

Hom.:

5184

Cov.:

AF XY:

0.0804

AC XY:

58379

AN XY:

726238

show subpopulations

African (AFR)

AF:

0.0119

AC:

399

AN:

33472

American (AMR)

AF:

0.0340

AC:

1520

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

3538

AN:

26120

East Asian (EAS)

AF:

0.128

AC:

5079

AN:

39688

South Asian (SAS)

AF:

0.0628

AC:

5414

AN:

86248

European-Finnish (FIN)

AF:

0.125

AC:

6482

AN:

51978

Middle Eastern (MID)

AF:

0.0392

AC:

226

AN:

5768

European-Non Finnish (NFE)

AF:

0.0808

AC:

89849

AN:

1111492

Other (OTH)

AF:

0.0787

AC:

4752

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

5984

11967

17951

23934

29918

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3282

6564

9846

13128

16410

<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:

0.0669

AC:

10182

AN:

152200

Hom.:

475

Cov.:

AF XY:

0.0679

AC XY:

5052

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0139

AC:

579

AN:

41554

American (AMR)

AF:

0.0464

AC:

710

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

489

AN:

3470

East Asian (EAS)

AF:

0.119

AC:

616

AN:

5156

South Asian (SAS)

AF:

0.0594

AC:

287

AN:

4828

European-Finnish (FIN)

AF:

0.139

AC:

1473

AN:

10580

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0866

AC:

5892

AN:

67998

Other (OTH)

AF:

0.0553

AC:

117

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

468

936

1405

1873

2341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0756

Hom.:

982

Bravo

AF:

0.0562

Asia WGS

AF:

0.0920

AC:

322

AN:

3478

EpiCase

AF:

0.0778

EpiControl

AF:

0.0746

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 7% of total chromosomes in ExAC -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.3

(source)

DANN

Benign

0.55

PhyloP100

0.14

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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