5-180638103-C-T

Variant names:

• chr5-180638103-C-T
• rs4700966
• NM_182925.5:c.59-6325G>A

Variant summary

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

The NM_182925.5(FLT4):​c.59-6325G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,008 control chromosomes in the GnomAD database, including 54,662 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 0.84 (54662 hom., cov: 31)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.75
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5	c.59-6325G>A		intron_variant	Intron 1 of 29	ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.59-6325G>A		intron_variant	Intron 1 of 29	1	NM_182925.5	ENSP00000261937.6

Frequencies

GnomAD3 genomes AF: 0.842 AC: 127938 AN: 151890 Hom.: 54630 Cov.: 31

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.894

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.914

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.894

Gnomad OTH AF: 0.863

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

GnomAD4 genome AF: 0.842 AC: 128021 AN: 152008 Hom.: 54662 Cov.: 31 AF XY: 0.846 AC XY: 62882 AN XY: 74300

African (AFR) AF: 0.686 AC: 28413 AN: 41418

American (AMR) AF: 0.908 AC: 13859 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.894 AC: 3103 AN: 3472

East Asian (EAS) AF: 0.980 AC: 5040 AN: 5144

South Asian (SAS) AF: 0.914 AC: 4399 AN: 4812

European-Finnish (FIN) AF: 0.915 AC: 9691 AN: 10594

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.894 AC: 60773 AN: 67980

Other (OTH) AF: 0.864 AC: 1825 AN: 2112

Alfa AF: 0.864 Hom.: 7413

Bravo AF: 0.835

Asia WGS AF: 0.933 AC: 3246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.16
DANN	Benign	0.71
PhyloP100		-3.8
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: rs4700966; hg19: chr5-180065103;