Genetic Variant FLT1:c.1437-4032G>C (chr13-28409926-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002019.4(FLT1):c.1437-4032G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,382 control chromosomes in the GnomAD database, including 7,098 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7098 hom., cov: 30)

Consequence

FLT1
NM_002019.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.150

Publications

20 publications found

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]

FLT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002019.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLT1	NM_002019.4	MANE Select	c.1437-4032G>C	intron	N/A	NP_002010.2	P17948-1
FLT1	NM_001160030.2		c.1437-4032G>C	intron	N/A	NP_001153502.1	P17948-3
FLT1	NM_001159920.2		c.1437-4032G>C	intron	N/A	NP_001153392.1	P17948-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FLT1	ENST00000282397.9	TSL:1 MANE Select	c.1437-4032G>C	intron	N/A	ENSP00000282397.4	P17948-1
FLT1	ENST00000541932.5	TSL:1	c.1437-4032G>C	intron	N/A	ENSP00000437631.1	P17948-3
FLT1	ENST00000615840.5	TSL:1	c.1437-4032G>C	intron	N/A	ENSP00000484039.1	P17948-2

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45293

AN:

151264

Hom.:

7094

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.294

Gnomad EAS

AF:

0.484

Gnomad SAS

AF:

0.302

Gnomad FIN

AF:

0.399

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.285

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.299

AC:

45314

AN:

151382

Hom.:

7098

Cov.:

AF XY:

0.301

AC XY:

22256

AN XY:

73928

show subpopulations

African (AFR)

AF:

0.278

AC:

11462

AN:

41200

American (AMR)

AF:

0.223

AC:

3403

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

1020

AN:

3464

East Asian (EAS)

AF:

0.483

AC:

2480

AN:

5136

South Asian (SAS)

AF:

0.303

AC:

1446

AN:

4776

European-Finnish (FIN)

AF:

0.399

AC:

4148

AN:

10386

Middle Eastern (MID)

AF:

0.241

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.301

AC:

20412

AN:

67874

Other (OTH)

AF:

0.289

AC:

608

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1546

3092

4637

6183

7729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.292

Hom.:

786

Bravo

AF:

0.286

Asia WGS

AF:

0.372

AC:

1293

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over