dbSNP rs7993418: FLT1:p.Tyr1213Tyr (chr13-28308924-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002019.4(FLT1):c.3639C>T(p.Tyr1213Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,585,192 control chromosomes in the GnomAD database, including 500,586 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 0.69 ( 39117 hom., cov: 32)

Exomes 𝑓: 0.80 ( 461469 hom. )

Consequence

FLT1
NM_002019.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.51

Publications

59 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:

ENSG00000307511 (HGNC:):

ENSG00000307511 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP7

Synonymous conserved (PhyloP=-1.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4 link	c.3639C>T	p.Tyr1213Tyr	synonymous_variant	Exon 28 of 30	ENST00000282397.9	NP_002010.2	P17948-1L7RSL3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9 link	c.3639C>T	p.Tyr1213Tyr	synonymous_variant	Exon 28 of 30	1	NM_002019.4	ENSP00000282397.4		P17948-1

Frequencies

GnomAD3 genomes

AF:

0.686

AC:

104284

AN:

151964

Hom.:

39100

Cov.:

show subpopulations

Gnomad AFR

AF:

0.356

Gnomad AMI

AF:

0.726

Gnomad AMR

AF:

0.815

Gnomad ASJ

AF:

0.854

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.895

Gnomad FIN

AF:

0.795

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.792

Gnomad OTH

AF:

0.731

GnomAD2 exomes

AF:

0.804

AC:

202061

AN:

251330

AF XY:

0.812

show subpopulations

Gnomad AFR exome

AF:

0.345

Gnomad AMR exome

AF:

0.874

Gnomad ASJ exome

AF:

0.850

Gnomad EAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.784

Gnomad NFE exome

AF:

0.794

Gnomad OTH exome

AF:

0.793

GnomAD4 exome

AF:

0.798

AC:

1143133

AN:

1433110

Hom.:

461469

Cov.:

AF XY:

0.801

AC XY:

573000

AN XY:

715002

show subpopulations

African (AFR)

AF:

0.337

AC:

11148

AN:

33124

American (AMR)

AF:

0.867

AC:

38716

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.849

AC:

22051

AN:

25962

East Asian (EAS)

AF:

0.999

AC:

39576

AN:

39604

South Asian (SAS)

AF:

0.882

AC:

75575

AN:

85682

European-Finnish (FIN)

AF:

0.786

AC:

41937

AN:

53364

Middle Eastern (MID)

AF:

0.712

AC:

4069

AN:

5716

European-Non Finnish (NFE)

AF:

0.795

AC:

863362

AN:

1085600

Other (OTH)

AF:

0.786

AC:

46699

AN:

59386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

9613

19226

28838

38451

48064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19996

39992

59988

79984

99980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.686

AC:

104336

AN:

152082

Hom.:

39117

Cov.:

AF XY:

0.696

AC XY:

51752

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.356

AC:

14768

AN:

41434

American (AMR)

AF:

0.816

AC:

12475

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.854

AC:

2964

AN:

3470

East Asian (EAS)

AF:

0.997

AC:

5169

AN:

5186

South Asian (SAS)

AF:

0.896

AC:

4325

AN:

4826

European-Finnish (FIN)

AF:

0.795

AC:

8392

AN:

10562

Middle Eastern (MID)

AF:

0.687

AC:

202

AN:

294

European-Non Finnish (NFE)

AF:

0.792

AC:

53836

AN:

68006

Other (OTH)

AF:

0.733

AC:

1543

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1355

2710

4064

5419

6774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.746

Hom.:

80627

Bravo

AF:

0.671

Asia WGS

AF:

0.917

AC:

3189

AN:

3478

EpiCase

AF:

0.793

EpiControl

AF:

0.791

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.10

(source)

DANN

Benign

0.45

PhyloP100

-1.5

PromoterAI

-0.025

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over