NM_182925.5:c.400+17G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182925.5(FLT4):c.400+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 1,612,380 control chromosomes in the GnomAD database, including 3,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 434 hom., cov: 32)

Exomes 𝑓: 0.018 ( 3104 hom. )

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.51

Publications

6 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 5-180630538-C-T is Benign according to our data. Variant chr5-180630538-C-T is described in CliVar as Benign. Clinvar id is 263058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180630538-C-T is described in CliVar as Benign. Clinvar id is 263058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180630538-C-T is described in CliVar as Benign. Clinvar id is 263058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180630538-C-T is described in CliVar as Benign. Clinvar id is 263058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180630538-C-T is described in CliVar as Benign. Clinvar id is 263058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180630538-C-T is described in CliVar as Benign. Clinvar id is 263058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180630538-C-T is described in CliVar as Benign. Clinvar id is 263058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180630538-C-T is described in CliVar as Benign. Clinvar id is 263058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180630538-C-T is described in CliVar as Benign. Clinvar id is 263058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180630538-C-T is described in CliVar as Benign. Clinvar id is 263058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180630538-C-T is described in CliVar as Benign. Clinvar id is 263058.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.400+17G>A		intron_variant	Intron 3 of 29	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.400+17G>A		intron_variant	Intron 3 of 29	1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.0224

AC:

3402

AN:

152044

Hom.:

428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0219

Gnomad ASJ

AF:

0.0262

Gnomad EAS

AF:

0.398

Gnomad SAS

AF:

0.0260

Gnomad FIN

AF:

0.0428

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00344

Gnomad OTH

AF:

0.0240

GnomAD2 exomes

AF:

0.0490

AC:

12137

AN:

247934

AF XY:

0.0450

show subpopulations

Gnomad AFR exome

AF:

0.00207

Gnomad AMR exome

AF:

0.0573

Gnomad ASJ exome

AF:

0.0291

Gnomad EAS exome

AF:

0.429

Gnomad FIN exome

AF:

0.0416

Gnomad NFE exome

AF:

0.00474

Gnomad OTH exome

AF:

0.0295

GnomAD4 exome

AF:

0.0180

AC:

26319

AN:

1460218

Hom.:

3104

Cov.:

AF XY:

0.0179

AC XY:

12995

AN XY:

726416

show subpopulations

African (AFR)

AF:

0.00218

AC:

AN:

33472

American (AMR)

AF:

0.0513

AC:

2294

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.0281

AC:

734

AN:

26122

East Asian (EAS)

AF:

0.377

AC:

14950

AN:

39638

South Asian (SAS)

AF:

0.0162

AC:

1394

AN:

86232

European-Finnish (FIN)

AF:

0.0392

AC:

2040

AN:

52068

Middle Eastern (MID)

AF:

0.0291

AC:

168

AN:

5768

European-Non Finnish (NFE)

AF:

0.00268

AC:

2981

AN:

1111874

Other (OTH)

AF:

0.0279

AC:

1685

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1388

2775

4163

5550

6938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.0225

AC:

3421

AN:

152162

Hom.:

434

Cov.:

AF XY:

0.0266

AC XY:

1980

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

41522

American (AMR)

AF:

0.0222

AC:

340

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0262

AC:

AN:

3472

East Asian (EAS)

AF:

0.399

AC:

2039

AN:

5116

South Asian (SAS)

AF:

0.0263

AC:

127

AN:

4834

European-Finnish (FIN)

AF:

0.0428

AC:

454

AN:

10610

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00344

AC:

234

AN:

67996

Other (OTH)

AF:

0.0304

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

132

264

396

528

660

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0153

Hom.:

Bravo

AF:

0.0266

Asia WGS

AF:

0.169

AC:

585

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.38

(source)

DANN

Benign

0.69

PhyloP100

-1.5

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