rs670084

Positions:

• chr13-28475647-C-A
• chr13-28475647-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002019.4(FLT1):​c.65-8030G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,064 control chromosomes in the GnomAD database, including 3,148 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 0.16 (3148 hom., cov: 32)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.592

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT1	NM_002019.4	c.65-8030G>T		intron_variant		ENST00000282397.9	NP_002010.2
FLT1	NM_001159920.2	c.65-8030G>T		intron_variant			NP_001153392.1
FLT1	NM_001160030.2	c.65-8030G>T		intron_variant			NP_001153502.1
FLT1	NM_001160031.1	c.65-8030G>T		intron_variant			NP_001153503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.65-8030G>T		intron_variant		1	NM_002019.4	ENSP00000282397	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24662 AN: 151946 Hom.: 3136 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0487

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0467

Gnomad FIN AF: 0.0919

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0893

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.163 AC: 24719 AN: 152064 Hom.: 3148 Cov.: 32 AF XY: 0.160 AC XY: 11871 AN XY: 74330

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.0487

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0465

Gnomad4 FIN AF: 0.0919

Gnomad4 NFE AF: 0.0893

Gnomad4 OTH AF: 0.136

Alfa AF: 0.0779 Hom.: 113

Bravo AF: 0.177

Asia WGS AF: 0.0400 AC: 137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.1
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs670084; hg19: chr13-29049784;