chr5-180614662-G-A

Variant names:

• chr5-180614662-G-A
• rs400330
• NM_182925.5:c.3220-483C>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.3220-483C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 151,808 control chromosomes in the GnomAD database, including 30,613 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 0.63 (30613 hom., cov: 31)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683
• Publications: 21 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5	c.3220-483C>T		intron_variant	Intron 23 of 29	ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.3220-483C>T		intron_variant	Intron 23 of 29	1	NM_182925.5	ENSP00000261937.6

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95619 AN: 151690 Hom.: 30597 Cov.: 31

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.630 AC: 95676 AN: 151808 Hom.: 30613 Cov.: 31 AF XY: 0.633 AC XY: 46954 AN XY: 74192

African (AFR) AF: 0.555 AC: 22977 AN: 41382

American (AMR) AF: 0.707 AC: 10788 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1973 AN: 3472

East Asian (EAS) AF: 0.473 AC: 2419 AN: 5118

South Asian (SAS) AF: 0.620 AC: 2982 AN: 4808

European-Finnish (FIN) AF: 0.712 AC: 7523 AN: 10564

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.660 AC: 44827 AN: 67890

Other (OTH) AF: 0.633 AC: 1334 AN: 2108

Alfa AF: 0.648 Hom.: 87716

Bravo AF: 0.625

Asia WGS AF: 0.555 AC: 1929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.45
PhyloP100		-0.68
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: rs400330; hg19: chr5-180041662;