13-28311673-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.10

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]

ACMG classification

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 GnomAd at 302 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00199 AC: 302 AN: 152134 Hom.: 1 Cov.: 32

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.: 0 AF XY: 0.00185 AC XY: 252 AN XY: 135856

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.: 13 Cov.: 32 AF XY: 0.00279 AC XY: 2031 AN XY: 726938

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.: 1 Cov.: 32 AF XY: 0.00187 AC XY: 139 AN XY: 74442

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.: 2

Bravo AF: 0.00207

EpiCase AF: 0.00376

EpiControl AF: 0.00397

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	FLT1: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jul 25, 2018	- -

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

Other links and lift over

dbSNP: rs55673217; hg19: chr13-28885810; COSMIC: COSV56744641; COSMIC: COSV56744641;