5-180619209-C-T

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.2761+44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 1,433,730 control chromosomes in the GnomAD database, including 339,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33116 hom., cov: 33)

Exomes 𝑓: 0.69 ( 306060 hom. )

Consequence

FLT4
NM_182925.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.99

Publications

7 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=-0.82).

BP6

Variant 5-180619209-C-T is Benign according to our data. Variant chr5-180619209-C-T is described in ClinVar as Benign. ClinVar VariationId is 263040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.2761+44G>A		intron_variant	Intron 19 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.2761+44G>A		intron_variant	Intron 19 of 29	1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.660

AC:

99091

AN:

150196

Hom.:

33088

Cov.:

show subpopulations

Gnomad AFR

AF:

0.600

Gnomad AMI

AF:

0.734

Gnomad AMR

AF:

0.728

Gnomad ASJ

AF:

0.652

Gnomad EAS

AF:

0.504

Gnomad SAS

AF:

0.650

Gnomad FIN

AF:

0.727

Gnomad MID

AF:

0.647

Gnomad NFE

AF:

0.682

Gnomad OTH

AF:

0.672

GnomAD2 exomes

AF:

0.712

AC:

91712

AN:

128860

AF XY:

0.705

show subpopulations

Gnomad AFR exome

AF:

0.645

Gnomad AMR exome

AF:

0.817

Gnomad ASJ exome

AF:

0.696

Gnomad EAS exome

AF:

0.555

Gnomad FIN exome

AF:

0.746

Gnomad NFE exome

AF:

0.711

Gnomad OTH exome

AF:

0.707

GnomAD4 exome

AF:

0.689

AC:

884712

AN:

1283426

Hom.:

306060

Cov.:

AF XY:

0.688

AC XY:

435977

AN XY:

633262

show subpopulations

African (AFR)

AF:

0.603

AC:

15391

AN:

25516

American (AMR)

AF:

0.802

AC:

20133

AN:

25100

Ashkenazi Jewish (ASJ)

AF:

0.684

AC:

14191

AN:

20746

East Asian (EAS)

AF:

0.508

AC:

14359

AN:

28252

South Asian (SAS)

AF:

0.662

AC:

43397

AN:

65548

European-Finnish (FIN)

AF:

0.736

AC:

32651

AN:

44336

Middle Eastern (MID)

AF:

0.619

AC:

2842

AN:

4592

European-Non Finnish (NFE)

AF:

0.694

AC:

706641

AN:

1017964

Other (OTH)

AF:

0.683

AC:

35107

AN:

51372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

12547

25094

37642

50189

62736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18780

37560

56340

75120

93900

<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:

0.660

AC:

99163

AN:

150304

Hom.:

33116

Cov.:

AF XY:

0.661

AC XY:

48568

AN XY:

73442

show subpopulations

African (AFR)

AF:

0.600

AC:

24778

AN:

41266

American (AMR)

AF:

0.728

AC:

11006

AN:

15108

Ashkenazi Jewish (ASJ)

AF:

0.652

AC:

2256

AN:

3460

East Asian (EAS)

AF:

0.503

AC:

2563

AN:

5094

South Asian (SAS)

AF:

0.651

AC:

3141

AN:

4822

European-Finnish (FIN)

AF:

0.727

AC:

7126

AN:

9798

Middle Eastern (MID)

AF:

0.648

AC:

188

AN:

290

European-Non Finnish (NFE)

AF:

0.682

AC:

46039

AN:

67464

Other (OTH)

AF:

0.668

AC:

1398

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1765

3530

5295

7060

8825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<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:

0.617

Hom.:

3383

Bravo

AF:

0.655

Asia WGS

AF:

0.598

AC:

2065

AN:

3454

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

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

-0.82

CADD

Benign

0.21

(source)

DANN

Benign

0.81

PhyloP100

-3.0

PromoterAI

0.0066

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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