5-180606031-G-A

Variant names:

• chr5-180606031-G-A
• rs13172346
• NM_182925.5:c.3894-2641C>T

Variant summary

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

The NM_182925.5(FLT4):​c.3894-2641C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,144 control chromosomes in the GnomAD database, including 2,229 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 0.16 (2229 hom., cov: 33)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	NM_182925.5	MANE Select	c.3894-2641C>T		intron	N/A	NP_891555.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	ENST00000261937.11	TSL:1 MANE Select	c.3894-2641C>T		intron	N/A	ENSP00000261937.6
	FLT4	ENST00000502603.5	TSL:2	n.594-2641C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24043 AN: 152026 Hom.: 2231 Cov.: 33

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0767

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.158 AC: 24039 AN: 152144 Hom.: 2229 Cov.: 33 AF XY: 0.159 AC XY: 11812 AN XY: 74370

African (AFR) AF: 0.0689 AC: 2861 AN: 41530

American (AMR) AF: 0.160 AC: 2438 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3472

East Asian (EAS) AF: 0.0771 AC: 399 AN: 5174

South Asian (SAS) AF: 0.192 AC: 925 AN: 4822

European-Finnish (FIN) AF: 0.183 AC: 1934 AN: 10576

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14227 AN: 67976

Other (OTH) AF: 0.173 AC: 366 AN: 2110

Alfa AF: 0.144 Hom.: 722

Bravo AF: 0.150

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.45
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13172346; hg19: chr5-180033031;