Genetic Variant FLT4:c.*1475A>G (chr5-180601717-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182925.5(FLT4):c.*1475A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 233,120 control chromosomes in the GnomAD database, including 75,327 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.77 ( 47018 hom., cov: 31)

Exomes 𝑓: 0.83 ( 28309 hom. )

Consequence

FLT4
NM_182925.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.05

Publications

15 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.*1475A>G		3_prime_UTR_variant	Exon 30 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.*1475A>G		3_prime_UTR_variant	Exon 30 of 30	1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.770

AC:

116932

AN:

151902

Hom.:

46990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.922

Gnomad AMR

AF:

0.746

Gnomad ASJ

AF:

0.856

Gnomad EAS

AF:

0.667

Gnomad SAS

AF:

0.770

Gnomad FIN

AF:

0.892

Gnomad MID

AF:

0.820

Gnomad NFE

AF:

0.899

Gnomad OTH

AF:

0.778

GnomAD4 exome

AF:

0.827

AC:

67065

AN:

81100

Hom.:

28309

Cov.:

AF XY:

0.830

AC XY:

30957

AN XY:

37290

show subpopulations

African (AFR)

AF:

0.523

AC:

2039

AN:

3898

American (AMR)

AF:

0.726

AC:

1814

AN:

2500

Ashkenazi Jewish (ASJ)

AF:

0.858

AC:

4400

AN:

5126

East Asian (EAS)

AF:

0.613

AC:

6999

AN:

11414

South Asian (SAS)

AF:

0.750

AC:

528

AN:

704

European-Finnish (FIN)

AF:

0.871

AC:

AN:

Middle Eastern (MID)

AF:

0.816

AC:

403

AN:

494

European-Non Finnish (NFE)

AF:

0.901

AC:

45145

AN:

50126

Other (OTH)

AF:

0.839

AC:

5683

AN:

6776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

637

1274

1911

2548

3185

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<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:

0.770

AC:

117003

AN:

152020

Hom.:

47018

Cov.:

AF XY:

0.769

AC XY:

57146

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.535

AC:

22161

AN:

41414

American (AMR)

AF:

0.746

AC:

11410

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.856

AC:

2973

AN:

3472

East Asian (EAS)

AF:

0.668

AC:

3439

AN:

5148

South Asian (SAS)

AF:

0.770

AC:

3712

AN:

4818

European-Finnish (FIN)

AF:

0.892

AC:

9437

AN:

10580

Middle Eastern (MID)

AF:

0.820

AC:

241

AN:

294

European-Non Finnish (NFE)

AF:

0.899

AC:

61150

AN:

67984

Other (OTH)

AF:

0.777

AC:

1639

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1215

2431

3646

4862

6077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.846

Hom.:

99741

Bravo

AF:

0.749

Asia WGS

AF:

0.697

AC:

2423

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.16

(source)

DANN

Benign

0.23

PhyloP100

-1.1

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

Computational scores

Splicing

Publications

Other links and lift over