chr5-180640675-G-A

Variant names:

• chr5-180640675-G-A
• rs307806
• NM_182925.5:c.58+8813C>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+8813C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,288 control chromosomes in the GnomAD database, including 1,808 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 0.15 (1808 hom., cov: 34)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.394
• 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 (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5	c.58+8813C>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+8813C>T		intron_variant	Intron 1 of 29	1	NM_182925.5	ENSP00000261937.6

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22486 AN: 152170 Hom.: 1802 Cov.: 34

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0505

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.148 AC: 22513 AN: 152288 Hom.: 1808 Cov.: 34 AF XY: 0.146 AC XY: 10905 AN XY: 74458

African (AFR) AF: 0.196 AC: 8145 AN: 41562

American (AMR) AF: 0.104 AC: 1589 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 562 AN: 3472

East Asian (EAS) AF: 0.0501 AC: 259 AN: 5172

South Asian (SAS) AF: 0.202 AC: 973 AN: 4828

European-Finnish (FIN) AF: 0.102 AC: 1081 AN: 10614

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9298 AN: 68012

Other (OTH) AF: 0.145 AC: 306 AN: 2116

Alfa AF: 0.141 Hom.: 2553

Bravo AF: 0.149

Asia WGS AF: 0.138 AC: 479 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	2.7
DANN	Benign	0.51
PhyloP100		0.39
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: rs307806; hg19: chr5-180067675;