chr5-180644276-G-A

Variant names:

• chr5-180644276-G-A
• rs11960332
• NM_182925.5:c.58+5212C>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.58+5212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,258 control chromosomes in the GnomAD database, including 2,450 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 (2450 hom., cov: 34)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5	c.58+5212C>T		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.58+5212C>T		intron_variant	Intron 1 of 29	1	NM_182925.5	ENSP00000261937.6

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24248 AN: 152140 Hom.: 2442 Cov.: 34

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.159 AC: 24272 AN: 152258 Hom.: 2450 Cov.: 34 AF XY: 0.162 AC XY: 12060 AN XY: 74460

African (AFR) AF: 0.141 AC: 5853 AN: 41552

American (AMR) AF: 0.247 AC: 3770 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2727 AN: 5166

South Asian (SAS) AF: 0.197 AC: 952 AN: 4826

European-Finnish (FIN) AF: 0.116 AC: 1228 AN: 10614

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.132 AC: 8953 AN: 68016

Other (OTH) AF: 0.158 AC: 334 AN: 2114

Alfa AF: 0.151 Hom.: 5415

Bravo AF: 0.178

Asia WGS AF: 0.325 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.52
PhyloP100		0.10
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: rs11960332; hg19: chr5-180071276;