ENST00000615840.5:c.*1172A>G

Variant names:

• chr13-28388529-T-C
• rs7337610
• ENST00000615840.5:c.*1172A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000615840.5(FLT1):​c.*1172A>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 0.602 in 1,040,722 control chromosomes in the GnomAD database, including 192,004 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 0.52 (21739 hom., cov: 31)
  • Exomes 𝑓: 0.62 (170265 hom.)
• Consequence: FLT1 ENST00000615840.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 18 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=-0.7).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.1969+1267A>G		intron_variant	Intron 13 of 29	ENST00000282397.9	NP_002010.2
FLT1	NM_001159920.2	c.*1172A>G		3_prime_UTR_variant	Exon 13 of 13		NP_001153392.1
FLT1	NM_001160030.2	c.1969+1267A>G		intron_variant	Intron 13 of 14		NP_001153502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000615840.5	c.*1172A>G		3_prime_UTR_variant	Exon 13 of 13	1		ENSP00000484039.1
FLT1	ENST00000282397.9	c.1969+1267A>G		intron_variant	Intron 13 of 29	1	NM_002019.4	ENSP00000282397.4
FLT1	ENST00000541932.5	c.1969+1267A>G		intron_variant	Intron 13 of 14	1		ENSP00000437631.1
FLT1	ENST00000639477.1	c.*1075A>G		3_prime_UTR_variant	Exon 14 of 14	5		ENSP00000491097.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78400 AN: 151802 Hom.: 21739 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.686

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.553

GnomAD4 exome AF: 0.617 AC: 548268 AN: 888802 Hom.: 170265 Cov.: 17 AF XY: 0.619 AC XY: 254346 AN XY: 410808

African (AFR) AF: 0.282 AC: 5291 AN: 18754

American (AMR) AF: 0.506 AC: 1454 AN: 2872

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 5779 AN: 9168

East Asian (EAS) AF: 0.553 AC: 7100 AN: 12832

South Asian (SAS) AF: 0.645 AC: 10880 AN: 16874

European-Finnish (FIN) AF: 0.550 AC: 177 AN: 322

Middle Eastern (MID) AF: 0.628 AC: 1238 AN: 1970

European-Non Finnish (NFE) AF: 0.626 AC: 496994 AN: 793688

Other (OTH) AF: 0.599 AC: 19355 AN: 32322

GnomAD4 genome AF: 0.516 AC: 78429 AN: 151920 Hom.: 21739 Cov.: 31 AF XY: 0.516 AC XY: 38326 AN XY: 74220

African (AFR) AF: 0.302 AC: 12516 AN: 41434

American (AMR) AF: 0.522 AC: 7968 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2285 AN: 3468

East Asian (EAS) AF: 0.532 AC: 2750 AN: 5166

South Asian (SAS) AF: 0.631 AC: 3033 AN: 4806

European-Finnish (FIN) AF: 0.550 AC: 5786 AN: 10526

Middle Eastern (MID) AF: 0.672 AC: 195 AN: 290

European-Non Finnish (NFE) AF: 0.620 AC: 42111 AN: 67948

Other (OTH) AF: 0.550 AC: 1161 AN: 2112

Alfa AF: 0.576 Hom.: 9844

Bravo AF: 0.505

Asia WGS AF: 0.577 AC: 2006 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Benign	0.85
PhyloP100		1.9
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: rs7337610; hg19: chr13-28962666;