Genetic Variant FLT1:p.Pro1068Pro (chr13-28319505-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002019.4(FLT1):c.3204T>C(p.Pro1068Pro) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -2.74

Publications

23 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 13-28319505-A-G is Benign according to our data. Variant chr13-28319505-A-G is described in ClinVar as Benign. ClinVar VariationId is 162072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.74 with no splicing effect.

BA1

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 rank	MANE	Protein	UniProt
FLT1	NM_002019.4 link	c.3204T>C	p.Pro1068Pro	synonymous_variant	Exon 24 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.3204T>C	p.Pro1068Pro	synonymous_variant	Exon 24 of 30	1	NM_002019.4	ENSP00000282397.4		P17948-1

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

32002

AN:

152058

Hom.:

3702

Cov.:

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

GnomAD2 exomes

AF:

0.206

AC:

51709

AN:

250682

AF XY:

0.218

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 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.:

AF XY:

0.208

AC XY:

150840

AN XY:

726356

show subpopulations

African (AFR)

AF:

0.272

AC:

9095

AN:

33434

American (AMR)

AF:

0.101

AC:

4537

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

6339

AN:

26106

East Asian (EAS)

AF:

0.161

AC:

6407

AN:

39684

South Asian (SAS)

AF:

0.407

AC:

35048

AN:

86102

European-Finnish (FIN)

AF:

0.134

AC:

7177

AN:

53388

Middle Eastern (MID)

AF:

0.259

AC:

1489

AN:

5760

European-Non Finnish (NFE)

AF:

0.189

AC:

209992

AN:

1110420

Other (OTH)

AF:

0.220

AC:

13245

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

10838

21676

32513

43351

54189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7522

15044

22566

30088

37610

<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:

0.210

AC:

32017

AN:

152176

Hom.:

3704

Cov.:

AF XY:

0.209

AC XY:

15524

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.275

AC:

11429

AN:

41508

American (AMR)

AF:

0.125

AC:

1920

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

875

AN:

3470

East Asian (EAS)

AF:

0.177

AC:

918

AN:

5180

South Asian (SAS)

AF:

0.406

AC:

1956

AN:

4816

European-Finnish (FIN)

AF:

0.123

AC:

1302

AN:

10586

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.188

AC:

12800

AN:

67998

Other (OTH)

AF:

0.209

AC:

441

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1288

2576

3865

5153

6441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.197

Hom.:

8152

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:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Carcinoma of colon

Other:1

Immunobiology Lab; University of Kashmir

Significance:not provided

Review Status:no classification provided

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.82

(source)

DANN

Benign

0.64

PhyloP100

-2.7

Mutation Taster

=93/7

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over