rs1130379

Variant names:

• chr5-180612606-C-A
• NM_182925.5:c.3437G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-180612606-C-A
• chr5-180612606-C-G
• chr5-180612606-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182925.5(FLT4):​c.3437G>T​(p.Arg1146Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,544 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1146H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FLT4 NM_182925.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.746

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5	c.3437G>T	p.Arg1146Leu	missense_variant	Exon 26 of 30	ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.3437G>T	p.Arg1146Leu	missense_variant	Exon 26 of 30	1	NM_182925.5	ENSP00000261937.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460544 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726710

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	9.1
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.58	D;.;D
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.81
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.76	T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.81	L;L;.
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.013	D;D;D
Sift4G	Benign	0.062	T;T;T
Polyphen		0.20	B;.;B
Vest4		0.58
MutPred		0.61		Loss of MoRF binding (P = 0.0092);Loss of MoRF binding (P = 0.0092);Loss of MoRF binding (P = 0.0092);
MVP		0.50
MPC		1.1
ClinPred		0.32	T
GERP RS		-0.63
Varity_R		0.23
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-180039606;