chr5-180629044-G-C

Variant names:

• chr5-180629044-G-C
• rs13359473
• NM_182925.5:c.986-45C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182925.5(FLT4):​c.986-45C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182925.5. 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
	FLT4	NM_182925.5	MANE Select	c.986-45C>G		intron	N/A	NP_891555.2
	FLT4	NM_001354989.2		c.986-45C>G		intron	N/A	NP_001341918.1
	FLT4	NM_002020.5		c.986-45C>G		intron	N/A	NP_002011.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	ENST00000261937.11	TSL:1 MANE Select	c.986-45C>G		intron	N/A	ENSP00000261937.6
	FLT4	ENST00000502649.5	TSL:1	c.986-45C>G		intron	N/A	ENSP00000426057.1
	FLT4	ENST00000393347.7	TSL:1	c.986-45C>G		intron	N/A	ENSP00000377016.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1392796 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 696666

African (AFR) AF: 0.00 AC: 0 AN: 32076

American (AMR) AF: 0.00 AC: 0 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25674

East Asian (EAS) AF: 0.00 AC: 0 AN: 39316

South Asian (SAS) AF: 0.00 AC: 0 AN: 84874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1050648

Other (OTH) AF: 0.00 AC: 0 AN: 58062

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 939

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.25
PhyloP100		-0.83

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: rs13359473; hg19: chr5-180056044;