5-180602471-C-G

Variant names:

• chr5-180602471-C-G
• rs6877011
• NM_182925.5:c.*721G>C

Variant summary

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

The NM_182925.5(FLT4):​c.*721G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 397,128 control chromosomes in the GnomAD database, including 3,641 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 0.10 (1187 hom., cov: 32)
  • Exomes 𝑓: 0.099 (2454 hom.)
• Consequence: FLT4 NM_182925.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• Publications: 15 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=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182925.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	NM_182925.5	MANE Select	c.*721G>C		3_prime_UTR	Exon 30 of 30	NP_891555.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	ENST00000261937.11	TSL:1 MANE Select	c.*721G>C		3_prime_UTR	Exon 30 of 30	ENSP00000261937.6
	FLT4	ENST00000955857.1		c.*721G>C		3_prime_UTR	Exon 30 of 30	ENSP00000625916.1
	FLT4	ENST00000861588.1		c.*721G>C		3_prime_UTR	Exon 30 of 30	ENSP00000531647.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15354 AN: 152108 Hom.: 1181 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0753

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.0961

GnomAD4 exome AF: 0.0992 AC: 24302 AN: 244904 Hom.: 2454 Cov.: 0 AF XY: 0.0978 AC XY: 12149 AN XY: 124182

African (AFR) AF: 0.155 AC: 1110 AN: 7170

American (AMR) AF: 0.0627 AC: 464 AN: 7406

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 1086 AN: 9212

East Asian (EAS) AF: 0.399 AC: 9102 AN: 22812

South Asian (SAS) AF: 0.151 AC: 331 AN: 2186

European-Finnish (FIN) AF: 0.0677 AC: 1426 AN: 21048

Middle Eastern (MID) AF: 0.101 AC: 130 AN: 1284

European-Non Finnish (NFE) AF: 0.0579 AC: 9119 AN: 157520

Other (OTH) AF: 0.0943 AC: 1534 AN: 16266

GnomAD4 genome AF: 0.101 AC: 15372 AN: 152224 Hom.: 1187 Cov.: 32 AF XY: 0.103 AC XY: 7681 AN XY: 74420

African (AFR) AF: 0.152 AC: 6324 AN: 41520

American (AMR) AF: 0.0628 AC: 961 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3472

East Asian (EAS) AF: 0.389 AC: 2011 AN: 5166

South Asian (SAS) AF: 0.144 AC: 695 AN: 4816

European-Finnish (FIN) AF: 0.0753 AC: 799 AN: 10610

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0575 AC: 3910 AN: 68016

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.0778 Hom.: 83

Bravo AF: 0.106

Asia WGS AF: 0.268 AC: 935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.3
DANN	Benign	0.78
PhyloP100		-0.53
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: rs6877011; hg19: chr5-180029471; COSMIC: COSV56128143; COSMIC: COSV56128143;