Variant 5-180603325-C-T 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.3959G>A(p.Arg1320Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00414 in 1,613,938 control chromosomes in the GnomAD database, including 238 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 (★★).

Frequency

Genomes: 𝑓 0.023 ( 122 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 116 hom. )

Consequence

FLT4
NM_182925.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.230

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=0.003283918).

BP6

Variant 5-180603325-C-T is Benign according to our data. Variant chr5-180603325-C-T is described in ClinVar as [Benign]. Clinvar id is 263054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180603325-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0747 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.3959G>A	p.Arg1320Gln	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.3959G>A	p.Arg1320Gln	missense_variant	30/30	1	NM_182925.5	ENSP00000261937.6		P35916-2
FLT4	ENST00000502603.5 linkuse as main transcript	n.659G>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.0226

AC:

3447

AN:

152254

Hom.:

122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0771

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0131

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:

0.000132

Gnomad OTH

AF:

0.0191

GnomAD3 exomes

AF:

0.00567

AC:

1402

AN:

247296

Hom.:

AF XY:

0.00408

AC XY:

547

AN XY:

134160

show subpopulations

Gnomad AFR exome

AF:

0.0796

Gnomad AMR exome

AF:

0.00285

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000208

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00221

AC:

3237

AN:

1461566

Hom.:

116

Cov.:

AF XY:

0.00183

AC XY:

1332

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.0799

Gnomad4 AMR exome

AF:

0.00360

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000809

Gnomad4 OTH exome

AF:

0.00486

GnomAD4 genome

AF:

0.0226

AC:

3449

AN:

152372

Hom.:

122

Cov.:

AF XY:

0.0220

AC XY:

1640

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0769

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.00396

Hom.:

Bravo

AF:

0.0264

ESP6500AA

AF:

0.0708

AC:

312

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00676

AC:

821

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

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

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Sep 13, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.4

DANN

Benign

0.97

DEOGEN2

Benign

0.086

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0033

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.13

REVEL

Benign

0.092

Sift

Benign

0.37

Sift4G

Benign

0.52

Polyphen

0.11

Vest4

0.10

MVP

0.17

MPC

0.14

ClinPred

0.0015

GERP RS

-0.50

Varity_R

0.018

gMVP

0.23

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