5-180612606-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182925.5(FLT4):c.3437G>A(p.Arg1146His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0942 in 1,611,386 control chromosomes in the GnomAD database, including 8,199 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.071 ( 544 hom., cov: 32)

Exomes 𝑓: 0.097 ( 7655 hom. )

Consequence

FLT4
NM_182925.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.746

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00330472).

BP6

Variant 5-180612606-C-T is Benign according to our data. Variant chr5-180612606-C-T is described in ClinVar as [Benign]. Clinvar id is 263050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180612606-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.3437G>A	p.Arg1146His	missense_variant	Exon 26 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.3437G>A	p.Arg1146His	missense_variant	Exon 26 of 30	1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.0715

AC:

10873

AN:

152046

Hom.:

544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0192

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.0460

Gnomad ASJ

AF:

0.0776

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0321

Gnomad FIN

AF:

0.121

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0675

GnomAD3 exomes

AF:

0.0748

AC:

18772

AN:

251056

Hom.:

970

AF XY:

0.0747

AC XY:

10137

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.0161

Gnomad AMR exome

AF:

0.0352

Gnomad ASJ exome

AF:

0.0867

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0347

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.0783

GnomAD4 exome

AF:

0.0966

AC:

140933

AN:

1459222

Hom.:

7655

Cov.:

AF XY:

0.0947

AC XY:

68746

AN XY:

726100

show subpopulations

Gnomad4 AFR exome

AF:

0.0151

Gnomad4 AMR exome

AF:

0.0371

Gnomad4 ASJ exome

AF:

0.0868

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0364

Gnomad4 FIN exome

AF:

0.126

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.0836

GnomAD4 genome

AF:

0.0714

AC:

10869

AN:

152164

Hom.:

544

Cov.:

AF XY:

0.0689

AC XY:

5121

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0191

Gnomad4 AMR

AF:

0.0459

Gnomad4 ASJ

AF:

0.0776

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0324

Gnomad4 FIN

AF:

0.121

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.0668

Alfa

AF:

0.0978

Hom.:

1229

Bravo

AF:

0.0641

TwinsUK

AF:

0.111

AC:

413

ALSPAC

AF:

0.113

AC:

435

ESP6500AA

AF:

0.0216

AC:

ESP6500EA

AF:

0.100

AC:

860

ExAC

AF:

0.0755

AC:

9163

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0922

EpiControl

AF:

0.102

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.28

T;.;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.59

T;T;T

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.63

N;N;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.25

N;N;N

REVEL

Benign

0.094

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.17

T;T;T

Polyphen

0.0020

B;.;B

Vest4

0.11

MPC

0.76

ClinPred

0.0015

GERP RS

-0.63

Varity_R

0.031

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over