rs3751395

Variant names:

• chr13-28384818-C-A
• rs3751395
• NM_002019.4:c.2116+67G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-28384818-C-A
• chr13-28384818-C-G

Variant summary

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

The NM_002019.4(FLT1):​c.2116+67G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,453,928 control chromosomes in the GnomAD database, including 178,122 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 0.53 (21820 hom., cov: 32)
  • Exomes 𝑓: 0.48 (156302 hom.)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 17 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.629 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	NM_002019.4	MANE Select	c.2116+67G>T		intron	N/A	NP_002010.2	P17948-1
	FLT1	NM_001160030.2		c.2116+67G>T		intron	N/A	NP_001153502.1	P17948-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	ENST00000282397.9	TSL:1 MANE Select	c.2116+67G>T		intron	N/A	ENSP00000282397.4	P17948-1
	FLT1	ENST00000541932.5	TSL:1	c.2116+67G>T		intron	N/A	ENSP00000437631.1	P17948-3
	FLT1	ENST00000909998.1		c.2137+67G>T		intron	N/A	ENSP00000580057.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79964 AN: 151736 Hom.: 21785 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.546

GnomAD4 exome AF: 0.482 AC: 627958 AN: 1302074 Hom.: 156302 AF XY: 0.484 AC XY: 317958 AN XY: 656460

African (AFR) AF: 0.636 AC: 19183 AN: 30162

American (AMR) AF: 0.722 AC: 32024 AN: 44334

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 10488 AN: 25134

East Asian (EAS) AF: 0.666 AC: 25820 AN: 38756

South Asian (SAS) AF: 0.604 AC: 49857 AN: 82516

European-Finnish (FIN) AF: 0.377 AC: 20023 AN: 53078

Middle Eastern (MID) AF: 0.488 AC: 2526 AN: 5172

European-Non Finnish (NFE) AF: 0.455 AC: 440782 AN: 967848

Other (OTH) AF: 0.495 AC: 27255 AN: 55074

GnomAD4 genome AF: 0.527 AC: 80051 AN: 151854 Hom.: 21820 Cov.: 32 AF XY: 0.529 AC XY: 39268 AN XY: 74188

African (AFR) AF: 0.636 AC: 26316 AN: 41382

American (AMR) AF: 0.631 AC: 9628 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1471 AN: 3472

East Asian (EAS) AF: 0.628 AC: 3240 AN: 5160

South Asian (SAS) AF: 0.612 AC: 2945 AN: 4812

European-Finnish (FIN) AF: 0.369 AC: 3875 AN: 10498

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30820 AN: 67956

Other (OTH) AF: 0.543 AC: 1146 AN: 2110

Alfa AF: 0.489 Hom.: 27746

Bravo AF: 0.554

Asia WGS AF: 0.613 AC: 2137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.33
PhyloP100		0.31
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3751395;

hg19: chr13-28958955;

COSMIC: COSV56719104;

COSMIC: COSV56719104;