chr13-28454417-C-T

Variant names:

• chr13-28454417-C-T
• rs10507386
• NM_002019.4:c.388+12486G>A

Variant summary

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

The NM_002019.4(FLT1):​c.388+12486G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,140 control chromosomes in the GnomAD database, including 1,423 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 0.12 (1423 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.388+12486G>A		intron_variant	Intron 3 of 29	ENST00000282397.9	NP_002010.2
FLT1	NM_001160030.2	c.388+12486G>A		intron_variant	Intron 3 of 14		NP_001153502.1
FLT1	NM_001159920.2	c.388+12486G>A		intron_variant	Intron 3 of 12		NP_001153392.1
FLT1	NM_001160031.1	c.388+12486G>A		intron_variant	Intron 3 of 11		NP_001153503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.388+12486G>A		intron_variant	Intron 3 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18332 AN: 152026 Hom.: 1414 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.0562

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.0916

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0822

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.121 AC: 18380 AN: 152140 Hom.: 1423 Cov.: 32 AF XY: 0.121 AC XY: 9002 AN XY: 74376

African (AFR) AF: 0.185 AC: 7681 AN: 41476

American (AMR) AF: 0.202 AC: 3086 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 195 AN: 3470

East Asian (EAS) AF: 0.0413 AC: 214 AN: 5178

South Asian (SAS) AF: 0.0806 AC: 389 AN: 4824

European-Finnish (FIN) AF: 0.0916 AC: 970 AN: 10588

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0822 AC: 5591 AN: 67998

Other (OTH) AF: 0.106 AC: 224 AN: 2110

Alfa AF: 0.0962 Hom.: 2579

Bravo AF: 0.132

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.51
PhyloP100		-0.19
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: rs10507386; hg19: chr13-29028554;