chr13-28433593-A-G

Variant names:

• chr13-28433593-A-G
• rs9551471
• NM_002019.4:c.813+226T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-0.88).
• 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 rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.813+226T>C		intron_variant	Intron 6 of 29	ENST00000282397.9	NP_002010.2
FLT1	NM_001160030.2	c.813+226T>C		intron_variant	Intron 6 of 14		NP_001153502.1
FLT1	NM_001159920.2	c.813+226T>C		intron_variant	Intron 6 of 12		NP_001153392.1
FLT1	NM_001160031.1	c.813+226T>C		intron_variant	Intron 6 of 11		NP_001153503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.813+226T>C		intron_variant	Intron 6 of 29	1	NM_002019.4	ENSP00000282397.4

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

African (AFR) AF: 0.0981 AC: 4069 AN: 41486

American (AMR) AF: 0.249 AC: 3803 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1099 AN: 3472

East Asian (EAS) AF: 0.186 AC: 960 AN: 5174

South Asian (SAS) AF: 0.0914 AC: 439 AN: 4802

European-Finnish (FIN) AF: 0.253 AC: 2667 AN: 10542

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21072 AN: 67982

Other (OTH) AF: 0.238 AC: 502 AN: 2110

Alfa AF: 0.261 Hom.: 980

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
PhyloP100		0.018
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: rs9551471; hg19: chr13-29007730;