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13-28319505-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002019.4(FLT1):c.3204T>C(p.Pro1068=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,612,098 control chromosomes in the GnomAD database, including 36,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.21 ( 3704 hom., cov: 32)
Exomes 𝑓: 0.20 ( 32534 hom. )

Consequence

FLT1
NM_002019.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -2.74
Variant links:
Genes affected
FLT1 (HGNC:3763): (fms related receptor tyrosine kinase 1) This gene encodes a member of the vascular endothelial growth factor receptor (VEGFR) family. VEGFR family members are receptor tyrosine kinases (RTKs) which contain an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and a tyrosine kinase (TK) domain within the cytoplasmic domain. This protein binds to VEGFR-A, VEGFR-B and placental growth factor and plays an important role in angiogenesis and vasculogenesis. Expression of this receptor is found in vascular endothelial cells, placental trophoblast cells and peripheral blood monocytes. Multiple transcript variants encoding different isoforms have been found for this gene. Isoforms include a full-length transmembrane receptor isoform and shortened, soluble isoforms. The soluble isoforms are associated with the onset of pre-eclampsia.[provided by RefSeq, May 2009]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 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=-0.55).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 13-28319505-A-G is Benign according to our data. Variant chr13-28319505-A-G is described in ClinVar as [Benign]. Clinvar id is 162072.Status of the report is criteria_provided_single_submitter, 1 stars.
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=-2.74 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FLT1NM_002019.4 linkuse as main transcriptc.3204T>C p.Pro1068= synonymous_variant 24/30 ENST00000282397.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FLT1ENST00000282397.9 linkuse as main transcriptc.3204T>C p.Pro1068= synonymous_variant 24/301 NM_002019.4 P1P17948-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.210
AC:
32002
AN:
152058
Hom.:
3702
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.276
Gnomad AMI
AF:
0.308
Gnomad AMR
AF:
0.126
Gnomad ASJ
AF:
0.252
Gnomad EAS
AF:
0.177
Gnomad SAS
AF:
0.405
Gnomad FIN
AF:
0.123
Gnomad MID
AF:
0.320
Gnomad NFE
AF:
0.188
Gnomad OTH
AF:
0.208
GnomAD3 exomes
AF:
0.206
AC:
51709
AN:
250682
Hom.:
6408
AF XY:
0.218
AC XY:
29550
AN XY:
135472
show subpopulations
Gnomad AFR exome
AF:
0.272
Gnomad AMR exome
AF:
0.0958
Gnomad ASJ exome
AF:
0.240
Gnomad EAS exome
AF:
0.184
Gnomad SAS exome
AF:
0.411
Gnomad FIN exome
AF:
0.125
Gnomad NFE exome
AF:
0.191
Gnomad OTH exome
AF:
0.206
GnomAD4 exome
AF:
0.201
AC:
293329
AN:
1459922
Hom.:
32534
Cov.:
31
AF XY:
0.208
AC XY:
150840
AN XY:
726356
show subpopulations
Gnomad4 AFR exome
AF:
0.272
Gnomad4 AMR exome
AF:
0.101
Gnomad4 ASJ exome
AF:
0.243
Gnomad4 EAS exome
AF:
0.161
Gnomad4 SAS exome
AF:
0.407
Gnomad4 FIN exome
AF:
0.134
Gnomad4 NFE exome
AF:
0.189
Gnomad4 OTH exome
AF:
0.220
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.210
AC:
32017
AN:
152176
Hom.:
3704
Cov.:
32
AF XY:
0.209
AC XY:
15524
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.275
Gnomad4 AMR
AF:
0.125
Gnomad4 ASJ
AF:
0.252
Gnomad4 EAS
AF:
0.177
Gnomad4 SAS
AF:
0.406
Gnomad4 FIN
AF:
0.123
Gnomad4 NFE
AF:
0.188
Gnomad4 OTH
AF:
0.209
Alfa
AF:
0.194
Hom.:
5246
Bravo
AF:
0.208
Asia WGS
AF:
0.269
AC:
936
AN:
3478
EpiCase
AF:
0.198
EpiControl
AF:
0.202

ClinVar

Significance: Benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJul 13, 2018- -
Carcinoma of colon Other:1
not provided, no classification providednot providedImmunobiology Lab; University of Kashmir-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
Cadd
Benign
0.82
Dann
Benign
0.64

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: rs2296189; hg19: chr13-28893642; COSMIC: COSV56721986; API