rs111916034

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_182925.5(FLT4):c.1049A>T(p.Glu350Val) variant causes a missense change. The variant allele was found at a frequency of 0.000766 in 1,612,714 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 4 hom. )

Consequence

FLT4
NM_182925.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.63

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=0.010187268).

BP6

Variant 5-180628936-T-A is Benign according to our data. Variant chr5-180628936-T-A is described in ClinVar as [Benign]. Clinvar id is 263015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180628936-T-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00408 (621/152238) while in subpopulation AFR AF= 0.0142 (588/41544). AF 95% confidence interval is 0.0132. There are 3 homozygotes in gnomad4. There are 288 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5 linkuse as main transcript	c.1049A>T	p.Glu350Val	missense_variant	8/30	ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11 linkuse as main transcript	c.1049A>T	p.Glu350Val	missense_variant	8/30	1	NM_182925.5	P1	P35916-2

Frequencies

GnomAD3 genomes

AF:

0.00401

AC:

610

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00105

AC:

261

AN:

248500

Hom.:

AF XY:

0.000828

AC XY:

112

AN XY:

135284

show subpopulations

Gnomad AFR exome

AF:

0.0145

Gnomad AMR exome

AF:

0.000637

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.000824

GnomAD4 exome

AF:

0.000421

AC:

615

AN:

1460476

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

264

AN XY:

726524

show subpopulations

Gnomad4 AFR exome

AF:

0.0140

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00408

AC:

621

AN:

152238

Hom.:

Cov.:

AF XY:

0.00387

AC XY:

288

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0142

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00132

Hom.:

Bravo

AF:

0.00448

ESP6500AA

AF:

0.0148

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00123

AC:

149

Asia WGS

AF:

0.00144

AC:

AN:

3476

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.24

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.48

T;.;T

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.71

LIST_S2

Uncertain

0.88

D;D;D

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.6

L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Benign

0.20

Sift

Benign

0.030

D;D;D

Sift4G

Benign

0.065

T;T;T

Polyphen

0.13

B;.;B

Vest4

0.64

MVP

0.25

MPC

0.96

ClinPred

0.031

GERP RS

2.4

Varity_R

0.18

gMVP

0.77

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

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