rs7324547

Variant names:

• chr13-28355470-A-G
• rs7324547
• NM_002019.4:c.2248+2084T>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.2248+2084T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,100 control chromosomes in the GnomAD database, including 34,641 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 0.65 (34641 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282
• Publications: 13 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]

ENSG00000298851 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.2248+2084T>C		intron_variant	Intron 15 of 29	ENST00000282397.9	NP_002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.2248+2084T>C		intron_variant	Intron 15 of 29	1	NM_002019.4	ENSP00000282397.4
ENSG00000298851	ENST00000758418.1	n.286-2426A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98169 AN: 151982 Hom.: 34642 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.788

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.646 AC: 98197 AN: 152100 Hom.: 34641 Cov.: 32 AF XY: 0.645 AC XY: 47972 AN XY: 74350

African (AFR) AF: 0.342 AC: 14188 AN: 41434

American (AMR) AF: 0.640 AC: 9789 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2976 AN: 3472

East Asian (EAS) AF: 0.649 AC: 3359 AN: 5174

South Asian (SAS) AF: 0.736 AC: 3552 AN: 4824

European-Finnish (FIN) AF: 0.776 AC: 8196 AN: 10562

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.788 AC: 53616 AN: 68020

Other (OTH) AF: 0.692 AC: 1461 AN: 2112

Alfa AF: 0.758 Hom.: 73098

Bravo AF: 0.623

Asia WGS AF: 0.689 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.61
PhyloP100		-0.28
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: rs7324547; hg19: chr13-28929607;