rs1130378

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.3198C>T(p.Pro1066Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,613,624 control chromosomes in the GnomAD database, including 62,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4913 hom., cov: 32)

Exomes 𝑓: 0.28 ( 57192 hom. )

Consequence

FLT4
NM_182925.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.889

Publications

27 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=-0.49).

BP6

Variant 5-180616388-G-A is Benign according to our data. Variant chr5-180616388-G-A is described in ClinVar as Benign. ClinVar VariationId is 263044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.889 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.3198C>T	p.Pro1066Pro	synonymous_variant	Exon 23 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.3198C>T	p.Pro1066Pro	synonymous_variant	Exon 23 of 30	1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37313

AN:

152096

Hom.:

4917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.288

Gnomad OTH

AF:

0.262

GnomAD2 exomes

AF:

0.265

AC:

66588

AN:

251220

AF XY:

0.277

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.227

Gnomad NFE exome

AF:

0.287

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.277

AC:

405478

AN:

1461408

Hom.:

57192

Cov.:

AF XY:

0.281

AC XY:

204249

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.170

AC:

5704

AN:

33480

American (AMR)

AF:

0.178

AC:

7978

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

8170

AN:

26134

East Asian (EAS)

AF:

0.249

AC:

9886

AN:

39700

South Asian (SAS)

AF:

0.347

AC:

29919

AN:

86246

European-Finnish (FIN)

AF:

0.230

AC:

12230

AN:

53206

Middle Eastern (MID)

AF:

0.354

AC:

2044

AN:

5768

European-Non Finnish (NFE)

AF:

0.281

AC:

312603

AN:

1111776

Other (OTH)

AF:

0.281

AC:

16944

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

16987

33975

50962

67950

84937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10342

20684

31026

41368

51710

<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:

0.245

AC:

37310

AN:

152216

Hom.:

4913

Cov.:

AF XY:

0.245

AC XY:

18254

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.170

AC:

7046

AN:

41526

American (AMR)

AF:

0.219

AC:

3344

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.322

AC:

1119

AN:

3470

East Asian (EAS)

AF:

0.255

AC:

1323

AN:

5184

South Asian (SAS)

AF:

0.332

AC:

1601

AN:

4824

European-Finnish (FIN)

AF:

0.229

AC:

2427

AN:

10610

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.288

AC:

19578

AN:

67986

Other (OTH)

AF:

0.259

AC:

548

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1479

2957

4436

5914

7393

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

400

800

1200

1600

2000

<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:

0.271

Hom.:

5237

Bravo

AF:

0.238

Asia WGS

AF:

0.258

AC:

898

AN:

3478

EpiCase

AF:

0.295

EpiControl

AF:

0.295

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Congenital heart defects, multiple types, 7

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary lymphedema type I

Benign:1

Aug 10, 2021

Genome-Nilou Lab

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

-0.49

CADD

Benign

3.6

(source)

DANN

Benign

0.74

PhyloP100

-0.89

Mutation Taster

=98/2

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over