rs11747066

chr5-180605263-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182925.5(FLT4):c.3894-1873C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,158 control chromosomes in the GnomAD database, including 4,021 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 0.22 (4021 hom., cov: 33)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.3894-1873C>T		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.3894-1873C>T		intron_variant		1	NM_182925.5	P1
FLT4	ENST00000502603.5	n.594-1873C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33259 AN: 152040 Hom.: 4023 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.219 AC: 33256 AN: 152158 Hom.: 4021 Cov.: 33 AF XY: 0.220 AC XY: 16371 AN XY: 74406

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.237

Alfa AF: 0.251 Hom.: 4591

Bravo AF: 0.212

Asia WGS AF: 0.266 AC: 927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.7
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs11747066; hg19: chr5-180032263;