rs9551471

chr13-28433593-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002019.4(FLT1):c.813+226T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,046 control chromosomes in the GnomAD database, including 4,715 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 0.23 (4715 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT1	NM_002019.4	c.813+226T>C		intron_variant		ENST00000282397.9
FLT1	NM_001159920.2	c.813+226T>C		intron_variant
FLT1	NM_001160030.2	c.813+226T>C		intron_variant
FLT1	NM_001160031.1	c.813+226T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT1	ENST00000282397.9	c.813+226T>C		intron_variant		1	NM_002019.4	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35067 AN: 151928 Hom.: 4714 Cov.: 32

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.231 AC: 35062 AN: 152046 Hom.: 4715 Cov.: 32 AF XY: 0.225 AC XY: 16688 AN XY: 74292

Gnomad4 AFR AF: 0.0981

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.0914

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.238

Alfa AF: 0.266 Hom.: 977

Bravo AF: 0.229

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.1
Dann	Benign	0.47

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: rs9551471; hg19: chr13-29007730;