13-28327871-T-C

Variant names:

• chr13-28327871-T-C
• rs3794400
• NM_002019.4:c.2708-321A>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.2708-321A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 152,030 control chromosomes in the GnomAD database, including 41,483 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 0.72 (41483 hom., cov: 31)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.2708-321A>G		intron_variant	Intron 19 of 29	ENST00000282397.9	NP_002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.2708-321A>G		intron_variant	Intron 19 of 29	1	NM_002019.4	ENSP00000282397.4
FLT1	ENST00000540678.2	n.595-321A>G		intron_variant	Intron 6 of 16	1
FLT1	ENST00000615611.4	n.126-321A>G		intron_variant	Intron 1 of 11	1
FLT1	ENST00000706527.1	n.533-321A>G		intron_variant	Intron 5 of 15

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109607 AN: 151914 Hom.: 41467 Cov.: 31

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.721 AC: 109663 AN: 152030 Hom.: 41483 Cov.: 31 AF XY: 0.721 AC XY: 53595 AN XY: 74328

African (AFR) AF: 0.479 AC: 19857 AN: 41432

American (AMR) AF: 0.691 AC: 10558 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2990 AN: 3466

East Asian (EAS) AF: 0.882 AC: 4555 AN: 5162

South Asian (SAS) AF: 0.786 AC: 3784 AN: 4812

European-Finnish (FIN) AF: 0.829 AC: 8776 AN: 10586

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56563 AN: 67966

Other (OTH) AF: 0.755 AC: 1597 AN: 2114

Alfa AF: 0.802 Hom.: 79465

Bravo AF: 0.700

Asia WGS AF: 0.816 AC: 2836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		-0.0060
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: rs3794400; hg19: chr13-28902008;