rs6491283

Variant names:

• chr13-28403602-G-A
• rs6491283
• NM_002019.4:c.1551+2178C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-28403602-G-A
• chr13-28403602-G-C
• chr13-28403602-G-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.1551+2178C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 152,322 control chromosomes in the GnomAD database, including 70,211 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 0.96 (70211 hom., cov: 33)
• Consequence: FLT1 NM_002019.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• Publications: 2 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 (EAS) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT1	NM_002019.4	c.1551+2178C>T		intron_variant	Intron 11 of 29	ENST00000282397.9	NP_002010.2
FLT1	NM_001160030.2	c.1551+2178C>T		intron_variant	Intron 11 of 14		NP_001153502.1
FLT1	NM_001159920.2	c.1551+2178C>T		intron_variant	Intron 11 of 12		NP_001153392.1
FLT1	NM_001160031.1	c.1551+2178C>T		intron_variant	Intron 11 of 11		NP_001153503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT1	ENST00000282397.9	c.1551+2178C>T		intron_variant	Intron 11 of 29	1	NM_002019.4	ENSP00000282397.4

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145940 AN: 152204 Hom.: 70175 Cov.: 33

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.967

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.959 AC: 146034 AN: 152322 Hom.: 70211 Cov.: 33 AF XY: 0.960 AC XY: 71542 AN XY: 74490

African (AFR) AF: 0.879 AC: 36529 AN: 41544

American (AMR) AF: 0.977 AC: 14957 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3433 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5190 AN: 5190

South Asian (SAS) AF: 0.998 AC: 4820 AN: 4828

European-Finnish (FIN) AF: 0.998 AC: 10608 AN: 10630

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.989 AC: 67267 AN: 68042

Other (OTH) AF: 0.968 AC: 2040 AN: 2108

Alfa AF: 0.978 Hom.: 231740

Bravo AF: 0.953

Asia WGS AF: 0.990 AC: 3443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.82
DANN	Benign	0.47
PhyloP100		0.16
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: rs6491283; hg19: chr13-28977739;