13-28494902-G-A

Variant names:

• chr13-28494902-G-A
• rs55927955
• NM_002019.4:c.-59C>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.-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
• Publications: 4 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.177 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.-59C>T		5_prime_UTR	Exon 1 of 30	NP_002010.2
	FLT1	NM_001160030.2		c.-59C>T		5_prime_UTR	Exon 1 of 15	NP_001153502.1
	FLT1	NM_001159920.2		c.-59C>T		5_prime_UTR	Exon 1 of 13	NP_001153392.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	ENST00000282397.9	TSL:1 MANE Select	c.-59C>T		5_prime_UTR	Exon 1 of 30	ENSP00000282397.4
	FLT1	ENST00000541932.5	TSL:1	c.-59C>T		5_prime_UTR	Exon 1 of 15	ENSP00000437631.1
	FLT1	ENST00000615840.5	TSL:1	c.-59C>T		5_prime_UTR	Exon 1 of 13	ENSP00000484039.1

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

African (AFR) AF: 0.0143 AC: 360 AN: 25098

American (AMR) AF: 0.280 AC: 8532 AN: 30422

Ashkenazi Jewish (ASJ) AF: 0.0626 AC: 1436 AN: 22930

East Asian (EAS) AF: 0.0401 AC: 1193 AN: 29734

South Asian (SAS) AF: 0.0951 AC: 6921 AN: 72766

European-Finnish (FIN) AF: 0.0564 AC: 1967 AN: 34878

Middle Eastern (MID) AF: 0.0584 AC: 294 AN: 5030

European-Non Finnish (NFE) AF: 0.0766 AC: 73983 AN: 965368

Other (OTH) AF: 0.0779 AC: 4075 AN: 52312

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

African (AFR) AF: 0.0171 AC: 710 AN: 41554

American (AMR) AF: 0.183 AC: 2792 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 214 AN: 3470

East Asian (EAS) AF: 0.0531 AC: 273 AN: 5142

South Asian (SAS) AF: 0.0888 AC: 428 AN: 4822

European-Finnish (FIN) AF: 0.0538 AC: 570 AN: 10602

Middle Eastern (MID) AF: 0.0651 AC: 19 AN: 292

European-Non Finnish (NFE) AF: 0.0759 AC: 5162 AN: 67968

Other (OTH) AF: 0.0729 AC: 154 AN: 2112

Alfa AF: 0.0699 Hom.: 61

Bravo AF: 0.0778

Asia WGS AF: 0.0540 AC: 188 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	14
DANN	Benign	0.94
PhyloP100		1.5
PromoterAI		-0.040	Neutral
Mutation Taster		=298/2	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: rs55927955; hg19: chr13-29069039;