rs7326277

chr13-28302077-T-C

Variant summary

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

The NM_002019.4(FLT1):c.*1090A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 233,168 control chromosomes in the GnomAD database, including 6,792 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 0.21 (5346 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1446 hom.)
• Consequence: FLT1 NM_002019.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT1	NM_002019.4	c.*1090A>G		3_prime_UTR_variant	30/30	ENST00000282397.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT1	ENST00000282397.9	c.*1090A>G		3_prime_UTR_variant	30/30	1	NM_002019.4	P1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31953 AN: 152008 Hom.: 5335 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0985

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.153 AC: 12403 AN: 81044 Hom.: 1446 Cov.: 0 AF XY: 0.151 AC XY: 5646 AN XY: 37276

Gnomad4 AFR exome AF: 0.462

Gnomad4 AMR exome AF: 0.0958

Gnomad4 ASJ exome AF: 0.0713

Gnomad4 EAS exome AF: 0.328

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.210 AC: 32010 AN: 152124 Hom.: 5346 Cov.: 32 AF XY: 0.210 AC XY: 15653 AN XY: 74396

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0985

Gnomad4 OTH AF: 0.179

Alfa AF: 0.191 Hom.: 832

Bravo AF: 0.221

Asia WGS AF: 0.225 AC: 785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.7
Dann	Benign	0.65

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: rs7326277; hg19: chr13-28876214;