chr5-180621056-C-T

Variant names:

Variant summary

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

The ENST00000424276.6(FLT4):n.2217G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,611,708 control chromosomes in the GnomAD database, including 45,077 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4445 hom., cov: 34)

Exomes 𝑓: 0.23 ( 40632 hom. )

Consequence

FLT4
ENST00000424276.6 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.11

Publications

11 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=-0.96).

BP6

Variant 5-180621056-C-T is Benign according to our data. Variant chr5-180621056-C-T is described in CliVar as Benign. Clinvar id is 263034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180621056-C-T is described in CliVar as Benign. Clinvar id is 263034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180621056-C-T is described in CliVar as Benign. Clinvar id is 263034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180621056-C-T is described in CliVar as Benign. Clinvar id is 263034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180621056-C-T is described in CliVar as Benign. Clinvar id is 263034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180621056-C-T is described in CliVar as Benign. Clinvar id is 263034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180621056-C-T is described in CliVar as Benign. Clinvar id is 263034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180621056-C-T is described in CliVar as Benign. Clinvar id is 263034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180621056-C-T is described in CliVar as Benign. Clinvar id is 263034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180621056-C-T is described in CliVar as Benign. Clinvar id is 263034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180621056-C-T is described in CliVar as Benign. Clinvar id is 263034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.2168-49G>A		intron_variant	Intron 14 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.2168-49G>A		intron_variant	Intron 14 of 29	1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

36057

AN:

152058

Hom.:

4441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.216

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.287

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.236

GnomAD2 exomes

AF:

0.231

AC:

56869

AN:

246522

AF XY:

0.238

show subpopulations

Gnomad AFR exome

AF:

0.258

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.296

Gnomad EAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.169

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.247

GnomAD4 exome

AF:

0.233

AC:

339900

AN:

1459530

Hom.:

40632

Cov.:

AF XY:

0.236

AC XY:

171013

AN XY:

725940

show subpopulations

African (AFR)

AF:

0.265

AC:

8867

AN:

33454

American (AMR)

AF:

0.152

AC:

6802

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

7619

AN:

26102

East Asian (EAS)

AF:

0.248

AC:

9832

AN:

39662

South Asian (SAS)

AF:

0.294

AC:

25374

AN:

86200

European-Finnish (FIN)

AF:

0.170

AC:

8838

AN:

52042

Middle Eastern (MID)

AF:

0.328

AC:

1890

AN:

5764

European-Non Finnish (NFE)

AF:

0.230

AC:

256069

AN:

1111316

Other (OTH)

AF:

0.242

AC:

14609

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

15494

30989

46483

61978

77472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8808

17616

26424

35232

44040

<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:

0.237

AC:

36084

AN:

152178

Hom.:

4445

Cov.:

AF XY:

0.236

AC XY:

17570

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.260

AC:

10774

AN:

41498

American (AMR)

AF:

0.190

AC:

2911

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

1041

AN:

3472

East Asian (EAS)

AF:

0.252

AC:

1296

AN:

5152

South Asian (SAS)

AF:

0.285

AC:

1375

AN:

4828

European-Finnish (FIN)

AF:

0.171

AC:

1813

AN:

10610

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.237

AC:

16088

AN:

68000

Other (OTH)

AF:

0.234

AC:

494

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1477

2954

4432

5909

7386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.212

Hom.:

1356

Bravo

AF:

0.239

Asia WGS

AF:

0.250

AC:

873

AN:

3478

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

-0.96

CADD

Benign

1.5

(source)

DANN

Benign

0.51

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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