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rs75516704

chr5-180630249-G-Achr5-180630249-G-Cchr5-180630249-G-T

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

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-5.39 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
FLT4NM_182925.5 linkuse as main transcriptc.489C>T p.Pro163= synonymous_variant 4/30 ENST00000261937.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FLT4ENST00000261937.11 linkuse as main transcriptc.489C>T p.Pro163= synonymous_variant 4/301 NM_182925.5 P1P35916-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0271
AC:
4127
AN:
152142
Hom.:
185
Cov.:
32
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.:
93
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.:
35
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0272
AC:
4138
AN:
152260
Hom.:
186
Cov.:
32
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.:
41
Bravo
AF:
0.0310
Asia WGS
AF:
0.0200
AC:
68
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 submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
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
-0.90
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.

Other links and lift over

dbSNP: rs75516704; hg19: chr5-180057249; API