NM_002019.4:c.3635+319G>T

Variant names:

• chr13-28311271-C-A
• rs9582036
• NM_002019.4:c.3635+319G>T

Variant summary

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

The NM_002019.4(FLT1):​c.3635+319G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,138 control chromosomes in the GnomAD database, including 31,563 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 0.60 (31563 hom., cov: 34)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 60 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 (SAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002019.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	NM_002019.4	MANE Select	c.3635+319G>T		intron	N/A	NP_002010.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	ENST00000282397.9	TSL:1 MANE Select	c.3635+319G>T		intron	N/A	ENSP00000282397.4
	FLT1	ENST00000540678.2	TSL:1	n.1522+319G>T		intron	N/A
	FLT1	ENST00000543394.2	TSL:1	n.860+319G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91703 AN: 152020 Hom.: 31545 Cov.: 34

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.603 AC: 91745 AN: 152138 Hom.: 31563 Cov.: 34 AF XY: 0.613 AC XY: 45585 AN XY: 74376

African (AFR) AF: 0.247 AC: 10246 AN: 41478

American (AMR) AF: 0.745 AC: 11391 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2798 AN: 3470

East Asian (EAS) AF: 0.814 AC: 4209 AN: 5168

South Asian (SAS) AF: 0.853 AC: 4113 AN: 4820

European-Finnish (FIN) AF: 0.747 AC: 7912 AN: 10590

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.719 AC: 48919 AN: 68006

Other (OTH) AF: 0.647 AC: 1368 AN: 2116

Alfa AF: 0.588 Hom.: 16095

Bravo AF: 0.584

Asia WGS AF: 0.807 AC: 2804 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.74
PhyloP100		-2.2
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: rs9582036; hg19: chr13-28885408;