Variant 5-180603313-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182925.5(FLT4):c.3971G>T(p.Arg1324Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,613,696 control chromosomes in the GnomAD database, including 8,130 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1324P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.081 ( 567 hom., cov: 33)

Exomes 𝑓: 0.099 ( 7563 hom. )

Consequence

FLT4
NM_182925.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.34

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:

FLT4 (HGNC:):

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=0.0015855432).

BP6

Variant 5-180603313-C-A is Benign according to our data. Variant chr5-180603313-C-A is described in ClinVar as [Benign]. Clinvar id is 263057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180603313-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT4	NM_182925.5 linkuse as main transcript	c.3971G>T	p.Arg1324Leu	missense_variant	30/30	ENST00000261937.11	NP_891555.2	P35916-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11 linkuse as main transcript	c.3971G>T	p.Arg1324Leu	missense_variant	30/30	1	NM_182925.5	ENSP00000261937.6		P35916-2
FLT4	ENST00000502603.5 linkuse as main transcript	n.671G>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.0806

AC:

12274

AN:

152246

Hom.:

567

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0512

Gnomad AMI

AF:

0.297

Gnomad AMR

AF:

0.0613

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0409

Gnomad FIN

AF:

0.0860

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.0755

GnomAD3 exomes

AF:

0.0786

AC:

19397

AN:

246898

Hom.:

926

AF XY:

0.0794

AC XY:

10635

AN XY:

133964

show subpopulations

Gnomad AFR exome

AF:

0.0535

Gnomad AMR exome

AF:

0.0448

Gnomad ASJ exome

AF:

0.0986

Gnomad EAS exome

AF:

0.000656

Gnomad SAS exome

AF:

0.0441

Gnomad FIN exome

AF:

0.0940

Gnomad NFE exome

AF:

0.110

Gnomad OTH exome

AF:

0.0845

GnomAD4 exome

AF:

0.0985

AC:

143954

AN:

1461332

Hom.:

7563

Cov.:

AF XY:

0.0968

AC XY:

70361

AN XY:

726924

show subpopulations

Gnomad4 AFR exome

AF:

0.0525

Gnomad4 AMR exome

AF:

0.0471

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.0465

Gnomad4 FIN exome

AF:

0.0925

Gnomad4 NFE exome

AF:

0.110

Gnomad4 OTH exome

AF:

0.0882

GnomAD4 genome

AF:

0.0806

AC:

12283

AN:

152364

Hom.:

567

Cov.:

AF XY:

0.0790

AC XY:

5889

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0513

Gnomad4 AMR

AF:

0.0612

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0408

Gnomad4 FIN

AF:

0.0860

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.0747

Alfa

AF:

0.0742

Hom.:

158

Bravo

AF:

0.0794

TwinsUK

AF:

0.119

AC:

442

ALSPAC

AF:

0.107

AC:

413

ESP6500AA

AF:

0.0522

AC:

230

ESP6500EA

AF:

0.109

AC:

934

ExAC

AF:

0.0803

AC:

9752

EpiCase

AF:

0.111

EpiControl

AF:

0.108

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

GeneDx

Jan 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.0060

DANN

Benign

0.39

DEOGEN2

Benign

0.078

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

PrimateAI

Benign

0.24

PROVEAN

Benign

0.12

REVEL

Benign

0.068

Sift

Benign

0.65

Sift4G

Benign

0.66

Polyphen

0.0

Vest4

0.023

MPC

0.14

ClinPred

0.00030

GERP RS

-8.8

Varity_R

0.029

gMVP

0.13

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