rs1565818

Variant names:

• chr5-180605500-G-C
• rs1565818
• NM_182925.5:c.3894-2110C>G

Variant summary

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

The NM_182925.5(FLT4):​c.3894-2110C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 152,148 control chromosomes in the GnomAD database, including 545 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 0.072 (545 hom., cov: 33)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5	c.3894-2110C>G		intron_variant	Intron 29 of 29	ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.3894-2110C>G		intron_variant	Intron 29 of 29	1	NM_182925.5	ENSP00000261937.6
FLT4	ENST00000502603.5	n.594-2110C>G		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0718 AC: 10915 AN: 152030 Hom.: 545 Cov.: 33

Gnomad AFR AF: 0.0192

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0689

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

GnomAD4 genome AF: 0.0717 AC: 10911 AN: 152148 Hom.: 545 Cov.: 33 AF XY: 0.0693 AC XY: 5157 AN XY: 74388

Gnomad4 AFR AF: 0.0191

Gnomad4 AMR AF: 0.0466

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0332

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0682

Alfa AF: 0.0989 Hom.: 102

Bravo AF: 0.0641

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.58

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: rs1565818; hg19: chr5-180032500;