rs34255532

Positions:

Variant summary

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

The NM_182925.5(FLT4):c.2860C>T(p.Pro954Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0057 in 1,585,876 control chromosomes in the GnomAD database, including 36 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 0.0035 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 32 hom. )

Consequence

FLT4
NM_182925.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:7

Conservation

PhyloP100: 3.79

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=0.006272793).

BP6

Variant 5-180618911-G-A is Benign according to our data. Variant chr5-180618911-G-A is described in ClinVar as [Benign]. Clinvar id is 16264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180618911-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00346 (527/152298) while in subpopulation NFE AF= 0.00619 (421/68010). AF 95% confidence interval is 0.0057. There are 4 homozygotes in gnomad4. There are 225 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT4	NM_182925.5 linkuse as main transcript	c.2860C>T	p.Pro954Ser	missense_variant	21/30	ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11 linkuse as main transcript	c.2860C>T	p.Pro954Ser	missense_variant	21/30	1	NM_182925.5	ENSP00000261937	P1	P35916-2

Frequencies

GnomAD3 genomes

AF:

0.00346

AC:

527

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00619

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00354

AC:

681

AN:

192522

Hom.:

AF XY:

0.00372

AC XY:

393

AN XY:

105698

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.000228

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00410

Gnomad FIN exome

AF:

0.000472

Gnomad NFE exome

AF:

0.00600

Gnomad OTH exome

AF:

0.00422

GnomAD4 exome

AF:

0.00594

AC:

8519

AN:

1433578

Hom.:

Cov.:

AF XY:

0.00597

AC XY:

4242

AN XY:

710598

show subpopulations

Gnomad4 AFR exome

AF:

0.00115

Gnomad4 AMR exome

AF:

0.00166

Gnomad4 ASJ exome

AF:

0.000157

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00368

Gnomad4 FIN exome

AF:

0.000632

Gnomad4 NFE exome

AF:

0.00699

Gnomad4 OTH exome

AF:

0.00618

GnomAD4 genome

AF:

0.00346

AC:

527

AN:

152298

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

225

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00619

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00493

Hom.:

Bravo

AF:

0.00354

ESP6500AA

AF:

0.00163

AC:

ESP6500EA

AF:

0.00496

AC:

ExAC

AF:

0.00307

AC:

362

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	FLT4: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Capillary infantile hemangioma

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2002

- -

Colorectal cancer

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

Aug 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.40

T;.;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.69

T;T;T

MetaRNN

Benign

0.0063

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.80

N;N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.088

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.016

B;.;B

Vest4

0.23

MVP

0.41

MPC

0.78

ClinPred

0.011

GERP RS

4.0

Varity_R

0.15

gMVP

0.61

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

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