Variant rs75516704 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.489C>T(p.Pro163=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00678 in 1,612,428 control chromosomes in the GnomAD database, including 405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 186 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 219 hom. )

Consequence

FLT4
NM_182925.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.39

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=-0.9).

BP6

Variant 5-180630249-G-A is Benign according to our data. Variant chr5-180630249-G-A is described in ClinVar as [Benign]. Clinvar id is 263063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180630249-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0856 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.489C>T	p.Pro163=	synonymous_variant	4/30	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.489C>T	p.Pro163=	synonymous_variant	4/30	1	NM_182925.5	ENSP00000261937	P1	P35916-2

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

4127

AN:

152142

Hom.:

185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0880

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0310

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.0108

AC:

2694

AN:

249674

Hom.:

AF XY:

0.00999

AC XY:

1354

AN XY:

135560

show subpopulations

Gnomad AFR exome

AF:

0.0940

Gnomad AMR exome

AF:

0.00527

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0297

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000453

Gnomad OTH exome

AF:

0.00541

GnomAD4 exome

AF:

0.00466

AC:

6798

AN:

1460168

Hom.:

219

Cov.:

AF XY:

0.00507

AC XY:

3684

AN XY:

726386

show subpopulations

Gnomad4 AFR exome

AF:

0.0929

Gnomad4 AMR exome

AF:

0.00573

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0299

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000273

Gnomad4 OTH exome

AF:

0.00850

GnomAD4 genome

AF:

0.0272

AC:

4138

AN:

152260

Hom.:

186

Cov.:

AF XY:

0.0265

AC XY:

1974

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0880

Gnomad4 AMR

AF:

0.0164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0309

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0139

Hom.:

Bravo

AF:

0.0310

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000889

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

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.029

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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