rs2242215

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.2168-28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 1,610,814 control chromosomes in the GnomAD database, including 4,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.059 ( 330 hom., cov: 34)

Exomes 𝑓: 0.064 ( 3713 hom. )

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.443

Publications

9 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):

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

new If you want to explore the variant's impact on the transcript NM_182925.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 5-180621035-T-C is Benign according to our data. Variant chr5-180621035-T-C is described in ClinVar as Benign. ClinVar VariationId is 263033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182925.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLT4	NM_182925.5	MANE Select	c.2168-28A>G	intron	N/A	NP_891555.2	P35916-2
FLT4	NM_001354989.2		c.2168-28A>G	intron	N/A	NP_001341918.1	E9PD35
FLT4	NM_002020.5		c.2168-28A>G	intron	N/A	NP_002011.2	P35916-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLT4	ENST00000261937.11	TSL:1 MANE Select	c.2168-28A>G	intron	N/A	ENSP00000261937.6	P35916-2
FLT4	ENST00000502649.5	TSL:1	c.2168-28A>G	intron	N/A	ENSP00000426057.1	E9PD35
FLT4	ENST00000393347.7	TSL:1	c.2168-28A>G	intron	N/A	ENSP00000377016.3	P35916-1

Frequencies

GnomAD3 genomes

AF:

0.0586

AC:

8905

AN:

152028

Hom.:

327

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0457

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0382

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.0381

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0570

Gnomad OTH

AF:

0.0547

GnomAD2 exomes

AF:

0.0735

AC:

18119

AN:

246478

AF XY:

0.0778

show subpopulations

Gnomad AFR exome

AF:

0.0444

Gnomad AMR exome

AF:

0.0390

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.0372

Gnomad NFE exome

AF:

0.0572

Gnomad OTH exome

AF:

0.0710

GnomAD4 exome

AF:

0.0639

AC:

93197

AN:

1458668

Hom.:

3713

Cov.:

AF XY:

0.0663

AC XY:

48074

AN XY:

725332

show subpopulations

African (AFR)

AF:

0.0471

AC:

1577

AN:

33454

American (AMR)

AF:

0.0407

AC:

1818

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

2882

AN:

26106

East Asian (EAS)

AF:

0.187

AC:

7406

AN:

39606

South Asian (SAS)

AF:

0.132

AC:

11380

AN:

86180

European-Finnish (FIN)

AF:

0.0369

AC:

1919

AN:

52034

Middle Eastern (MID)

AF:

0.0861

AC:

496

AN:

5762

European-Non Finnish (NFE)

AF:

0.0554

AC:

61480

AN:

1110610

Other (OTH)

AF:

0.0703

AC:

4239

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

5087

10175

15262

20350

25437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2446

4892

7338

9784

12230

<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:

0.0586

AC:

8914

AN:

152146

Hom.:

330

Cov.:

AF XY:

0.0591

AC XY:

4396

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0459

AC:

1907

AN:

41526

American (AMR)

AF:

0.0380

AC:

581

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

405

AN:

3472

East Asian (EAS)

AF:

0.184

AC:

944

AN:

5136

South Asian (SAS)

AF:

0.135

AC:

653

AN:

4826

European-Finnish (FIN)

AF:

0.0381

AC:

404

AN:

10610

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0570

AC:

3875

AN:

67978

Other (OTH)

AF:

0.0551

AC:

116

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

442

884

1325

1767

2209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

220

330

440

550

<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:

0.0634

Hom.:

Bravo

AF:

0.0585

Asia WGS

AF:

0.133

AC:

465

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.9

(source)

DANN

Benign

0.32

PhyloP100

-0.44

La Branchor

0.71

BranchPoint Hunter

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over