rs3797104

chr5-180624987-T-C

Variant summary

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

The NM_182925.5(FLT4):c.1421+882A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,216 control chromosomes in the GnomAD database, including 2,137 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 0.16 (2137 hom., cov: 33)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.1421+882A>G		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.1421+882A>G		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23735 AN: 152096 Hom.: 2121 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.156 AC: 23797 AN: 152216 Hom.: 2137 Cov.: 33 AF XY: 0.156 AC XY: 11635 AN XY: 74414

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.172

Alfa AF: 0.127 Hom.: 1715

Bravo AF: 0.166

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.5
Dann	Benign	0.45

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: rs3797104; hg19: chr5-180051987; COSMIC: COSV56102583; COSMIC: COSV56102583;