dbSNP rs3736062: FLT4:p.Tyr448Tyr (chr5-180625946-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

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

The NM_182925.5(FLT4):c.1344C>T(p.Tyr448Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 1,612,724 control chromosomes in the GnomAD database, including 1,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 91 hom., cov: 33)

Exomes 𝑓: 0.031 ( 982 hom. )

Consequence

FLT4
NM_182925.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0300

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=-0.55).

BP6

Variant 5-180625946-G-A is Benign according to our data. Variant chr5-180625946-G-A is described in ClinVar as [Benign]. Clinvar id is 263024.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180625946-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.03 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0995 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5 link	c.1344C>T	p.Tyr448Tyr	synonymous_variant	Exon 10 of 30	ENST00000261937.11	NP_891555.2	P35916-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11 link	c.1344C>T	p.Tyr448Tyr	synonymous_variant	Exon 10 of 30	1	NM_182925.5	ENSP00000261937.6		P35916-2

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3907

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00623

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0298

Gnomad ASJ

AF:

0.0767

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0228

Gnomad FIN

AF:

0.0210

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.0289

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0318

AC:

7883

AN:

248152

Hom.:

226

AF XY:

0.0313

AC XY:

4225

AN XY:

134814

show subpopulations

Gnomad AFR exome

AF:

0.00684

Gnomad AMR exome

AF:

0.0188

Gnomad ASJ exome

AF:

0.0764

Gnomad EAS exome

AF:

0.109

Gnomad SAS exome

AF:

0.0208

Gnomad FIN exome

AF:

0.0192

Gnomad NFE exome

AF:

0.0279

Gnomad OTH exome

AF:

0.0335

GnomAD4 exome

AF:

0.0314

AC:

45819

AN:

1460438

Hom.:

982

Cov.:

AF XY:

0.0312

AC XY:

22658

AN XY:

726512

show subpopulations

Gnomad4 AFR exome

AF:

0.00508

Gnomad4 AMR exome

AF:

0.0200

Gnomad4 ASJ exome

AF:

0.0721

Gnomad4 EAS exome

AF:

0.121

Gnomad4 SAS exome

AF:

0.0192

Gnomad4 FIN exome

AF:

0.0190

Gnomad4 NFE exome

AF:

0.0299

Gnomad4 OTH exome

AF:

0.0350

GnomAD4 genome

AF:

0.0257

AC:

3909

AN:

152286

Hom.:

Cov.:

AF XY:

0.0246

AC XY:

1831

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00618

Gnomad4 AMR

AF:

0.0297

Gnomad4 ASJ

AF:

0.0767

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.0230

Gnomad4 FIN

AF:

0.0210

Gnomad4 NFE

AF:

0.0290

Gnomad4 OTH

AF:

0.0321

Alfa

AF:

0.0294

Hom.:

Bravo

AF:

0.0259

Asia WGS

AF:

0.0680

AC:

238

AN:

3478

EpiCase

AF:

0.0306

EpiControl

AF:

0.0316

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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: 3% of total chromosomes in ExAC, 11% of E. Asian chromosomes -

not provided

Benign:1

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.1

DANN

Benign

0.71

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