5-180603231-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1

The NM_182925.5(FLT4):​c.4053G>A​(p.Pro1351Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000436 in 1,614,120 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00043 ( 1 hom. )

Consequence

FLT4
NM_182925.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.27
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 -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
Variant 5-180603231-C-T is Benign according to our data. Variant chr5-180603231-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3250576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-4.27 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000453 (69/152368) while in subpopulation EAS AF= 0.00251 (13/5182). AF 95% confidence interval is 0.00148. There are 0 homozygotes in gnomad4. There are 40 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FLT4NM_182925.5 linkc.4053G>A p.Pro1351Pro synonymous_variant Exon 30 of 30 ENST00000261937.11 NP_891555.2 P35916-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FLT4ENST00000261937.11 linkc.4053G>A p.Pro1351Pro synonymous_variant Exon 30 of 30 1 NM_182925.5 ENSP00000261937.6 P35916-2
FLT4ENST00000502603.5 linkn.753G>A non_coding_transcript_exon_variant Exon 4 of 4 2

Frequencies

GnomAD3 genomes
AF:
0.000460
AC:
70
AN:
152250
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00270
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00358
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000849
AC:
212
AN:
249774
Hom.:
0
AF XY:
0.000820
AC XY:
111
AN XY:
135368
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00278
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00370
Gnomad NFE exome
AF:
0.000657
Gnomad OTH exome
AF:
0.000818
GnomAD4 exome
AF:
0.000434
AC:
635
AN:
1461752
Hom.:
1
Cov.:
31
AF XY:
0.000428
AC XY:
311
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00234
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00390
Gnomad4 NFE exome
AF:
0.000257
Gnomad4 OTH exome
AF:
0.000580
GnomAD4 genome
AF:
0.000453
AC:
69
AN:
152368
Hom.:
0
Cov.:
33
AF XY:
0.000537
AC XY:
40
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00251
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00358
Gnomad4 NFE
AF:
0.000220
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000259
Hom.:
0
Bravo
AF:
0.000253
Asia WGS
AF:
0.00289
AC:
10
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Nov 13, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1
Jun 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

FLT4: BP4, BP7, BS1 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.18
DANN
Benign
0.54

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: rs2270519; hg19: chr5-180030231; COSMIC: COSV56114191; COSMIC: COSV56114191; API