chr5-180641741-G-A

Variant names:

• chr5-180641741-G-A
• rs11748431
• NM_182925.5:c.58+7747C>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+7747C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,164 control chromosomes in the GnomAD database, including 3,684 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 0.21 (3684 hom., cov: 33)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5	c.58+7747C>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+7747C>T		intron_variant	Intron 1 of 29	1	NM_182925.5	ENSP00000261937.6

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31818 AN: 152046 Hom.: 3688 Cov.: 33

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.209 AC: 31825 AN: 152164 Hom.: 3684 Cov.: 33 AF XY: 0.208 AC XY: 15510 AN XY: 74396

African (AFR) AF: 0.149 AC: 6169 AN: 41530

American (AMR) AF: 0.192 AC: 2935 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 754 AN: 3472

East Asian (EAS) AF: 0.0212 AC: 110 AN: 5186

South Asian (SAS) AF: 0.172 AC: 827 AN: 4818

European-Finnish (FIN) AF: 0.227 AC: 2409 AN: 10596

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17750 AN: 67960

Other (OTH) AF: 0.221 AC: 466 AN: 2110

Alfa AF: 0.247 Hom.: 17672

Bravo AF: 0.202

Asia WGS AF: 0.102 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.79
PhyloP100		-0.0010
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: rs11748431; hg19: chr5-180068741;