rs2296283

Variant names:

• chr13-28389565-G-A
• rs2296283
• ENST00000615840.5:c.*136C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-28389565-G-A
• chr13-28389565-G-C
• chr13-28389565-G-T

Variant summary

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

The NM_001159920.2(FLT1):​c.*136C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 1,435,328 control chromosomes in the GnomAD database, including 197,498 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 0.42 (15610 hom., cov: 32)
  • Exomes 𝑓: 0.53 (181888 hom.)
• Consequence: FLT1 NM_001159920.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.823
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159920.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	NM_002019.4	MANE Select	c.1969+231C>T		intron	N/A	NP_002010.2	P17948-1
	FLT1	NM_001159920.2		c.*136C>T		3_prime_UTR	Exon 13 of 13	NP_001153392.1	P17948-2
	FLT1	NM_001160030.2		c.1969+231C>T		intron	N/A	NP_001153502.1	P17948-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	ENST00000615840.5	TSL:1	c.*136C>T		3_prime_UTR	Exon 13 of 13	ENSP00000484039.1	P17948-2
	FLT1	ENST00000282397.9	TSL:1 MANE Select	c.1969+231C>T		intron	N/A	ENSP00000282397.4	P17948-1
	FLT1	ENST00000541932.5	TSL:1	c.1969+231C>T		intron	N/A	ENSP00000437631.1	P17948-3

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64502 AN: 152008 Hom.: 15614 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.462

GnomAD4 exome AF: 0.528 AC: 678128 AN: 1283202 Hom.: 181888 Cov.: 49 AF XY: 0.530 AC XY: 329222 AN XY: 621488

African (AFR) AF: 0.166 AC: 4677 AN: 28226

American (AMR) AF: 0.454 AC: 8862 AN: 19524

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 10928 AN: 18904

East Asian (EAS) AF: 0.556 AC: 19394 AN: 34882

South Asian (SAS) AF: 0.502 AC: 30470 AN: 60750

European-Finnish (FIN) AF: 0.459 AC: 14725 AN: 32082

Middle Eastern (MID) AF: 0.529 AC: 1904 AN: 3600

European-Non Finnish (NFE) AF: 0.543 AC: 560025 AN: 1031866

Other (OTH) AF: 0.509 AC: 27143 AN: 53368

GnomAD4 genome AF: 0.424 AC: 64512 AN: 152126 Hom.: 15610 Cov.: 32 AF XY: 0.423 AC XY: 31469 AN XY: 74390

African (AFR) AF: 0.176 AC: 7323 AN: 41506

American (AMR) AF: 0.453 AC: 6921 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2072 AN: 3468

East Asian (EAS) AF: 0.528 AC: 2721 AN: 5154

South Asian (SAS) AF: 0.495 AC: 2386 AN: 4820

European-Finnish (FIN) AF: 0.466 AC: 4927 AN: 10584

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.536 AC: 36469 AN: 67988

Other (OTH) AF: 0.459 AC: 970 AN: 2114

Alfa AF: 0.436 Hom.: 2270

Bravo AF: 0.415

Asia WGS AF: 0.504 AC: 1751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		0.82
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: rs2296283; hg19: chr13-28963702;