Genetic Variant FLT1:c.1660+180G>A (chr13-28396780-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002019.4(FLT1):c.1660+180G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.977 in 695,840 control chromosomes in the GnomAD database, including 332,786 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 0.95 ( 68947 hom., cov: 29)

Exomes 𝑓: 0.98 ( 263839 hom. )

Consequence

FLT1
NM_002019.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.298

Variant links:

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]

FLT1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4 link	c.1660+180G>A	intron_variant	Intron 12 of 29	ENST00000282397.9	NP_002010.2	P17948-1L7RSL3
FLT1	NM_001160030.2 link	c.1660+180G>A	intron_variant	Intron 12 of 14		NP_001153502.1	P17948-3
FLT1	NM_001159920.2 link	c.1660+180G>A	intron_variant	Intron 12 of 12		NP_001153392.1	P17948-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9 link	c.1660+180G>A		intron_variant	Intron 12 of 29	1	NM_002019.4	ENSP00000282397.4		P17948-1

Frequencies

GnomAD3 genomes

AF:

0.950

AC:

144391

AN:

151960

Hom.:

68907

Cov.:

show subpopulations

Gnomad AFR

AF:

0.851

Gnomad AMI

AF:

0.996

Gnomad AMR

AF:

0.975

Gnomad ASJ

AF:

0.989

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.979

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.988

Gnomad OTH

AF:

0.963

GnomAD3 exomes

AF:

0.981

AC:

134139

AN:

136722

Hom.:

65864

AF XY:

0.983

AC XY:

72085

AN XY:

73364

show subpopulations

Gnomad AFR exome

AF:

0.854

Gnomad AMR exome

AF:

0.987

Gnomad ASJ exome

AF:

0.986

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.984

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.988

Gnomad OTH exome

AF:

0.981

GnomAD4 exome

AF:

0.985

AC:

535502

AN:

543762

Hom.:

263839

Cov.:

AF XY:

0.985

AC XY:

290542

AN XY:

294836

show subpopulations

Gnomad4 AFR exome

AF:

0.860

Gnomad4 AMR exome

AF:

0.985

Gnomad4 ASJ exome

AF:

0.986

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.985

Gnomad4 FIN exome

AF:

0.998

Gnomad4 NFE exome

AF:

0.989

Gnomad4 OTH exome

AF:

0.978

GnomAD4 genome

AF:

0.950

AC:

144490

AN:

152078

Hom.:

68947

Cov.:

AF XY:

0.952

AC XY:

70759

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.851

Gnomad4 AMR

AF:

0.975

Gnomad4 ASJ

AF:

0.989

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.979

Gnomad4 FIN

AF:

0.998

Gnomad4 NFE

AF:

0.988

Gnomad4 OTH

AF:

0.963

Alfa

AF:

0.963

Hom.:

14213

Bravo

AF:

0.944

Asia WGS

AF:

0.978

AC:

3401

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.8

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over