rs307805

Variant names:

• chr5-180650487-T-C
• rs307805
• XM_017009268.2:c.-289A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-180650487-T-C
• chr5-180650487-T-G

Variant summary

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

The XM_017009268.2(FLT4):​c.-289A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,862 control chromosomes in the GnomAD database, including 1,830 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 0.14 (1830 hom., cov: 30)
• Consequence: FLT4 XM_017009268.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 17 publications found

Genes affected

FLT4 (HGNC:3767): (fms related receptor tyrosine kinase 4) This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA. [provided by RefSeq, Jul 2008]

FLT4 Gene-Disease associations (from GenCC):

• lymphatic malformation 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• capillary infantile hemangioma

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• congenital heart defects, multiple types, 7

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• lymphatic malformation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• tetralogy of fallot

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21607 AN: 151744 Hom.: 1823 Cov.: 30

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.0998

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0259

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.142 AC: 21627 AN: 151862 Hom.: 1830 Cov.: 30 AF XY: 0.142 AC XY: 10573 AN XY: 74256

African (AFR) AF: 0.223 AC: 9240 AN: 41356

American (AMR) AF: 0.0996 AC: 1519 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3470

East Asian (EAS) AF: 0.0256 AC: 132 AN: 5164

South Asian (SAS) AF: 0.211 AC: 1013 AN: 4802

European-Finnish (FIN) AF: 0.0824 AC: 869 AN: 10542

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.114 AC: 7761 AN: 67976

Other (OTH) AF: 0.130 AC: 273 AN: 2104

Alfa AF: 0.122 Hom.: 3648

Bravo AF: 0.146

Asia WGS AF: 0.137 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.66
PhyloP100		0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs307805; hg19: chr5-180077487;