13-28319347-T-C

Variant names:

• chr13-28319347-T-C
• rs2296188
• NM_002019.4:c.3286+76A>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.3286+76A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 994,850 control chromosomes in the GnomAD database, including 330,880 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 0.71 (40976 hom., cov: 31)
  • Exomes 𝑓: 0.82 (289904 hom.)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.610
• Publications: 16 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.3286+76A>G		intron_variant	Intron 24 of 29	ENST00000282397.9	NP_002010.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.3286+76A>G		intron_variant	Intron 24 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107661 AN: 151924 Hom.: 40962 Cov.: 31

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.733

GnomAD4 exome AF: 0.824 AC: 694877 AN: 842808 Hom.: 289904 AF XY: 0.822 AC XY: 359764 AN XY: 437638

African (AFR) AF: 0.404 AC: 8525 AN: 21124

American (AMR) AF: 0.829 AC: 29768 AN: 35922

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 17692 AN: 21610

East Asian (EAS) AF: 0.712 AC: 24636 AN: 34624

South Asian (SAS) AF: 0.725 AC: 49385 AN: 68150

European-Finnish (FIN) AF: 0.851 AC: 41035 AN: 48194

Middle Eastern (MID) AF: 0.703 AC: 2370 AN: 3370

European-Non Finnish (NFE) AF: 0.859 AC: 490064 AN: 570262

Other (OTH) AF: 0.794 AC: 31402 AN: 39552

GnomAD4 genome AF: 0.708 AC: 107712 AN: 152042 Hom.: 40976 Cov.: 31 AF XY: 0.708 AC XY: 52609 AN XY: 74342

African (AFR) AF: 0.406 AC: 16829 AN: 41406

American (AMR) AF: 0.766 AC: 11714 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2825 AN: 3468

East Asian (EAS) AF: 0.682 AC: 3525 AN: 5170

South Asian (SAS) AF: 0.709 AC: 3413 AN: 4812

European-Finnish (FIN) AF: 0.841 AC: 8901 AN: 10584

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.852 AC: 57927 AN: 68006

Other (OTH) AF: 0.731 AC: 1542 AN: 2108

Alfa AF: 0.806 Hom.: 98697

Bravo AF: 0.693

Asia WGS AF: 0.687 AC: 2393 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	1.1
DANN	Benign	0.60
PhyloP100		-0.61
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: rs2296188; hg19: chr13-28893484;