rs12429309

Variant names:

• chr13-28305195-T-C
• rs12429309
• NM_002019.4:c.3815+1483A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002019.4(FLT1):​c.3815+1483A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,096 control chromosomes in the GnomAD database, including 4,073 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 0.22 (4073 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.3815+1483A>G		intron_variant	Intron 29 of 29	ENST00000282397.9	NP_002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.3815+1483A>G		intron_variant	Intron 29 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34092 AN: 151978 Hom.: 4063 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.225 AC: 34150 AN: 152096 Hom.: 4073 Cov.: 32 AF XY: 0.226 AC XY: 16785 AN XY: 74370

African (AFR) AF: 0.245 AC: 10184 AN: 41488

American (AMR) AF: 0.312 AC: 4771 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3470

East Asian (EAS) AF: 0.278 AC: 1434 AN: 5166

South Asian (SAS) AF: 0.238 AC: 1148 AN: 4814

European-Finnish (FIN) AF: 0.202 AC: 2135 AN: 10584

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13036 AN: 67982

Other (OTH) AF: 0.181 AC: 382 AN: 2112

Alfa AF: 0.209 Hom.: 5185

Bravo AF: 0.237

Asia WGS AF: 0.292 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.61
PhyloP100		0.075
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12429309; hg19: chr13-28879332;