NM_182925.5:c.1344C>T

Variant names:

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.1344C>T(p.Tyr448Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,612,724 control chromosomes in the GnomAD database, including 1,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 91 hom., cov: 33)

Exomes 𝑓: 0.031 ( 982 hom. )

Consequence

FLT4
NM_182925.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0300

Publications

14 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=-0.55).

BP6

Variant 5-180625946-G-A is Benign according to our data. Variant chr5-180625946-G-A is described in ClinVar as Benign. ClinVar VariationId is 263024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0995 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.1344C>T	p.Tyr448Tyr	synonymous_variant	Exon 10 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.1344C>T	p.Tyr448Tyr	synonymous_variant	Exon 10 of 30	1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3907

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00623

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0298

Gnomad ASJ

AF:

0.0767

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.0210

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0289

Gnomad OTH

AF:

0.0301

GnomAD2 exomes

AF:

0.0318

AC:

7883

AN:

248152

AF XY:

0.0313

show subpopulations

Gnomad AFR exome

AF:

0.00684

Gnomad AMR exome

AF:

0.0188

Gnomad ASJ exome

AF:

0.0764

Gnomad EAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.0192

Gnomad NFE exome

AF:

0.0279

Gnomad OTH exome

AF:

0.0335

GnomAD4 exome

AF:

0.0314

AC:

45819

AN:

1460438

Hom.:

982

Cov.:

AF XY:

0.0312

AC XY:

22658

AN XY:

726512

show subpopulations

African (AFR)

AF:

0.00508

AC:

170

AN:

33480

American (AMR)

AF:

0.0200

AC:

895

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0721

AC:

1883

AN:

26130

East Asian (EAS)

AF:

0.121

AC:

4796

AN:

39698

South Asian (SAS)

AF:

0.0192

AC:

1660

AN:

86252

European-Finnish (FIN)

AF:

0.0190

AC:

988

AN:

52132

Middle Eastern (MID)

AF:

0.0207

AC:

119

AN:

5736

European-Non Finnish (NFE)

AF:

0.0299

AC:

33193

AN:

1111926

Other (OTH)

AF:

0.0350

AC:

2115

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

2762

5525

8287

11050

13812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1328

2656

3984

5312

6640

<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:

0.0257

AC:

3909

AN:

152286

Hom.:

Cov.:

AF XY:

0.0246

AC XY:

1831

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00618

AC:

257

AN:

41564

American (AMR)

AF:

0.0297

AC:

454

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0767

AC:

266

AN:

3470

East Asian (EAS)

AF:

0.107

AC:

552

AN:

5164

South Asian (SAS)

AF:

0.0230

AC:

111

AN:

4830

European-Finnish (FIN)

AF:

0.0210

AC:

223

AN:

10626

Middle Eastern (MID)

AF:

0.0308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0290

AC:

1969

AN:

68010

Other (OTH)

AF:

0.0321

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

211

421

632

842

1053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0300

Hom.:

Bravo

AF:

0.0259

Asia WGS

AF:

0.0680

AC:

238

AN:

3478

EpiCase

AF:

0.0306

EpiControl

AF:

0.0316

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: 3% of total chromosomes in ExAC, 11% of E. Asian chromosomes -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 09, 2021

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

-0.55

CADD

Benign

3.1

(source)

DANN

Benign

0.71

PhyloP100

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over