Variant rs1130378 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000261937.11(FLT4):c.3198C>T(p.Pro1066=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,613,624 control chromosomes in the GnomAD database, including 62,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4913 hom., cov: 32)

Exomes 𝑓: 0.28 ( 57192 hom. )

Consequence

FLT4
ENST00000261937.11 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.889

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 5-180616388-G-A is Benign according to our data. Variant chr5-180616388-G-A is described in ClinVar as [Benign]. Clinvar id is 263044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180616388-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.889 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 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.3198C>T	p.Pro1066=	synonymous_variant	23/30	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.3198C>T	p.Pro1066=	synonymous_variant	23/30	1	NM_182925.5	ENSP00000261937	P1	P35916-2

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37313

AN:

152096

Hom.:

4917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.255

Gnomad SAS

AF:

0.334

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.288

Gnomad OTH

AF:

0.262

GnomAD3 exomes

AF:

0.265

AC:

66588

AN:

251220

Hom.:

9391

AF XY:

0.277

AC XY:

37594

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.248

Gnomad SAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.227

Gnomad NFE exome

AF:

0.287

Gnomad OTH exome

AF:

0.292

GnomAD4 exome

AF:

0.277

AC:

405478

AN:

1461408

Hom.:

57192

Cov.:

AF XY:

0.281

AC XY:

204249

AN XY:

727018

show subpopulations

Gnomad4 AFR exome

AF:

0.170

Gnomad4 AMR exome

AF:

0.178

Gnomad4 ASJ exome

AF:

0.313

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.347

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.281

Gnomad4 OTH exome

AF:

0.281

GnomAD4 genome

AF:

0.245

AC:

37310

AN:

152216

Hom.:

4913

Cov.:

AF XY:

0.245

AC XY:

18254

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.219

Gnomad4 ASJ

AF:

0.322

Gnomad4 EAS

AF:

0.255

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.229

Gnomad4 NFE

AF:

0.288

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.270

Hom.:

4007

Bravo

AF:

0.238

Asia WGS

AF:

0.258

AC:

898

AN:

3478

EpiCase

AF:

0.295

EpiControl

AF:

0.295

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Congenital heart defects, multiple types, 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Hereditary lymphedema type I

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

3.6

DANN

Benign

0.74

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