rs3736062

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

2

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]

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/exons MANE Protein UniProt
FLT4NM_182925.5 linkuse as main transcriptc.1344C>T p.Tyr448Tyr synonymous_variant 10/30 ENST00000261937.11 NP_891555.2 P35916-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FLT4ENST00000261937.11 linkuse as main transcriptc.1344C>T p.Tyr448Tyr synonymous_variant 10/301 NM_182925.5 ENSP00000261937.6 P35916-2

Frequencies

GnomAD3 genomes
AF:
0.0257
AC:
3907
AN:
152168
Hom.:
90
Cov.:
33
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.:
33
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.:
91
Cov.:
33
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.:
40
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
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant 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
Benign, criteria provided, single submitterclinical testingGeneDxJun 09, 2021- -

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.

Other links and lift over

dbSNP: rs3736062; hg19: chr5-180052946; COSMIC: COSV56098092; COSMIC: COSV56098092; API