13-28320069-A-G

Variant names:

• chr13-28320069-A-G
• rs7987291
• NM_002019.4:c.3175-535T>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.3175-535T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,108 control chromosomes in the GnomAD database, including 5,690 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 0.26 (5690 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.789
• Publications: 8 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 (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.3175-535T>C		intron_variant	Intron 23 of 29	ENST00000282397.9	NP_002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.3175-535T>C		intron_variant	Intron 23 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39310 AN: 151988 Hom.: 5671 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.259 AC: 39367 AN: 152108 Hom.: 5690 Cov.: 32 AF XY: 0.259 AC XY: 19285 AN XY: 74366

African (AFR) AF: 0.397 AC: 16472 AN: 41458

American (AMR) AF: 0.172 AC: 2631 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 601 AN: 3470

East Asian (EAS) AF: 0.184 AC: 949 AN: 5168

South Asian (SAS) AF: 0.269 AC: 1295 AN: 4820

European-Finnish (FIN) AF: 0.217 AC: 2294 AN: 10586

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14409 AN: 68002

Other (OTH) AF: 0.241 AC: 510 AN: 2112

Alfa AF: 0.222 Hom.: 7414

Bravo AF: 0.259

Asia WGS AF: 0.207 AC: 719 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	9.0
DANN	Benign	0.69
PhyloP100		0.79
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: rs7987291; hg19: chr13-28894206; COSMIC: COSV56740484;