NM_182925.5:c.*60G>A

Variant names:

• chr5-180603132-C-T
• rs113034305
• NM_182925.5:c.*60G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182925.5(FLT4):​c.*60G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,549,076 control chromosomes in the GnomAD database, including 292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (113 hom., cov: 33)
  • Exomes 𝑓: 0.010 (179 hom.)
• Consequence: FLT4 NM_182925.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.238
• Publications: 1 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):

• congenital heart defects, multiple types, 7

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• lymphatic malformation 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• capillary infantile hemangioma

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 5-180603132-C-T is Benign according to our data. Variant chr5-180603132-C-T is described in ClinVar as Benign. ClinVar VariationId is 1274028.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0685 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.*60G>A		3_prime_UTR	Exon 30 of 30	NP_891555.2	P35916-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	ENST00000261937.11	TSL:1 MANE Select	c.*60G>A		3_prime_UTR	Exon 30 of 30	ENSP00000261937.6	P35916-2
	FLT4	ENST00000955857.1		c.*60G>A		3_prime_UTR	Exon 30 of 30	ENSP00000625916.1
	FLT4	ENST00000861588.1		c.*60G>A		3_prime_UTR	Exon 30 of 30	ENSP00000531647.1

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3955 AN: 152230 Hom.: 113 Cov.: 33

Gnomad AFR AF: 0.0703

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00641

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00925

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0103 AC: 14384 AN: 1396728 Hom.: 179 Cov.: 26 AF XY: 0.0102 AC XY: 7083 AN XY: 697174

African (AFR) AF: 0.0747 AC: 2408 AN: 32246

American (AMR) AF: 0.0102 AC: 441 AN: 43190

Ashkenazi Jewish (ASJ) AF: 0.00838 AC: 214 AN: 25546

East Asian (EAS) AF: 0.0000510 AC: 2 AN: 39246

South Asian (SAS) AF: 0.00545 AC: 457 AN: 83846

European-Finnish (FIN) AF: 0.00295 AC: 153 AN: 51856

Middle Eastern (MID) AF: 0.0199 AC: 107 AN: 5364

European-Non Finnish (NFE) AF: 0.00933 AC: 9861 AN: 1057258

Other (OTH) AF: 0.0127 AC: 741 AN: 58176

GnomAD4 genome AF: 0.0261 AC: 3978 AN: 152348 Hom.: 113 Cov.: 33 AF XY: 0.0258 AC XY: 1922 AN XY: 74506

African (AFR) AF: 0.0706 AC: 2935 AN: 41576

American (AMR) AF: 0.0169 AC: 259 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00642 AC: 31 AN: 4832

European-Finnish (FIN) AF: 0.00292 AC: 31 AN: 10630

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00925 AC: 629 AN: 68028

Other (OTH) AF: 0.0241 AC: 51 AN: 2116

Alfa AF: 0.0160 Hom.: 14

Bravo AF: 0.0289

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.2
DANN	Benign	0.83
PhyloP100		-0.24
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: rs113034305; hg19: chr5-180030132;