rs55927955

chr13-28494902-G-Achr13-28494902-G-C

Variant summary

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

The NM_002019.4(FLT1):c.-59C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 1,390,710 control chromosomes in the GnomAD database, including 5,548 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 0.068 (604 hom., cov: 33)
  • Exomes 𝑓: 0.080 (4944 hom.)
• Consequence: FLT1 NM_002019.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT1	NM_002019.4	c.-59C>T		5_prime_UTR_variant	1/30	ENST00000282397.9
FLT1	NM_001159920.2	c.-59C>T		5_prime_UTR_variant	1/13
FLT1	NM_001160030.2	c.-59C>T		5_prime_UTR_variant	1/15
FLT1	NM_001160031.1	c.-59C>T		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT1	ENST00000282397.9	c.-59C>T		5_prime_UTR_variant	1/30	1	NM_002019.4	P1
FLT1	ENST00000541932.5	c.-59C>T		5_prime_UTR_variant	1/15	1
FLT1	ENST00000615840.5	c.-59C>T		5_prime_UTR_variant	1/13	1
FLT1	ENST00000639477.1	c.-59C>T		5_prime_UTR_variant	1/14	5

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10328 AN: 152064 Hom.: 605 Cov.: 33

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.0527

Gnomad SAS AF: 0.0887

Gnomad FIN AF: 0.0538

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0760

Gnomad OTH AF: 0.0732

GnomAD4 exome AF: 0.0797 AC: 98761 AN: 1238538 Hom.: 4944 Cov.: 18 AF XY: 0.0795 AC XY: 48972 AN XY: 616186

Gnomad4 AFR exome AF: 0.0143

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.0626

Gnomad4 EAS exome AF: 0.0401

Gnomad4 SAS exome AF: 0.0951

Gnomad4 FIN exome AF: 0.0564

Gnomad4 NFE exome AF: 0.0766

Gnomad4 OTH exome AF: 0.0779

GnomAD4 genome AF: 0.0679 AC: 10332 AN: 152172 Hom.: 604 Cov.: 33 AF XY: 0.0693 AC XY: 5156 AN XY: 74386

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.0531

Gnomad4 SAS AF: 0.0888

Gnomad4 FIN AF: 0.0538

Gnomad4 NFE AF: 0.0759

Gnomad4 OTH AF: 0.0729

Alfa AF: 0.0715 Hom.: 61

Bravo AF: 0.0778

Asia WGS AF: 0.0540 AC: 188 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	14
Dann	Benign	0.94

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: rs55927955; hg19: chr13-29069039;