Variant 13-28311673-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002019.4(FLT1):c.3552C>T(p.Tyr1184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,613,416 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 13 hom. )

Consequence

FLT1
NM_002019.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.10

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 made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

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

BP6

Variant 13-28311673-G-A is Benign according to our data. Variant chr13-28311673-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 775340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.1 with no splicing effect.

BS2

High AC in GnomAd4 at 302 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT1	NM_002019.4 linkuse as main transcript	c.3552C>T	p.Tyr1184=	synonymous_variant	27/30	ENST00000282397.9	NP_002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9 linkuse as main transcript	c.3552C>T	p.Tyr1184=	synonymous_variant	27/30	1	NM_002019.4	ENSP00000282397	P1	P17948-1

Frequencies

GnomAD3 genomes

AF:

0.00199

AC:

302

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00317

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00176

AC:

443

AN:

251378

Hom.:

AF XY:

0.00185

AC XY:

252

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00300

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00281

AC:

4112

AN:

1461164

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

2031

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.00347

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.00198

AC:

302

AN:

152252

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00318

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00282

Hom.:

Bravo

AF:

0.00207

EpiCase

AF:

0.00376

EpiControl

AF:

0.00397

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 25, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	FLT1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.2

DANN

Benign

0.46

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over