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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	XM_017009268.2	c.-289A>G		upstream_gene_variant			XP_016864757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

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 v4.3

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;