Variant chr5-180630231-C-A 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 NM_182925.5(FLT4):c.507G>T(p.Leu169=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0791 in 1,612,042 control chromosomes in the GnomAD database, including 5,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 475 hom., cov: 32)

Exomes 𝑓: 0.080 ( 5184 hom. )

Consequence

FLT4
NM_182925.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.144

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=-0.51).

BP6

Variant 5-180630231-C-A is Benign according to our data. Variant chr5-180630231-C-A is described in ClinVar as [Benign]. Clinvar id is 263064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180630231-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.144 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5 linkuse as main transcript	c.507G>T	p.Leu169=	synonymous_variant	4/30	ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11 linkuse as main transcript	c.507G>T	p.Leu169=	synonymous_variant	4/30	1	NM_182925.5	P1	P35916-2

Frequencies

GnomAD3 genomes

AF:

0.0670

AC:

10183

AN:

152082

Hom.:

475

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0465

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.0590

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0867

Gnomad OTH

AF:

0.0535

GnomAD3 exomes

AF:

0.0766

AC:

19113

AN:

249510

Hom.:

875

AF XY:

0.0775

AC XY:

10501

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.0313

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.117

Gnomad SAS exome

AF:

0.0654

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.0800

Gnomad OTH exome

AF:

0.0760

GnomAD4 exome

AF:

0.0803

AC:

117259

AN:

1459842

Hom.:

5184

Cov.:

AF XY:

0.0804

AC XY:

58379

AN XY:

726238

show subpopulations

Gnomad4 AFR exome

AF:

0.0119

Gnomad4 AMR exome

AF:

0.0340

Gnomad4 ASJ exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.0628

Gnomad4 FIN exome

AF:

0.125

Gnomad4 NFE exome

AF:

0.0808

Gnomad4 OTH exome

AF:

0.0787

GnomAD4 genome

AF:

0.0669

AC:

10182

AN:

152200

Hom.:

475

Cov.:

AF XY:

0.0679

AC XY:

5052

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0139

Gnomad4 AMR

AF:

0.0464

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.0594

Gnomad4 FIN

AF:

0.139

Gnomad4 NFE

AF:

0.0866

Gnomad4 OTH

AF:

0.0553

Alfa

AF:

0.0780

Hom.:

843

Bravo

AF:

0.0562

Asia WGS

AF:

0.0920

AC:

322

AN:

3478

EpiCase

AF:

0.0778

EpiControl

AF:

0.0746

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 7% of total chromosomes in ExAC -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.3

DANN

Benign

0.55

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