rs2242208

chr5-180622907-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182925.5(FLT4):c.1549-68C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.045 in 1,069,728 control chromosomes in the GnomAD database, including 1,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (220 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1478 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.376

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-180622907-G-A is Benign according to our data. Variant chr5-180622907-G-A is described in ClinVar as [Benign]. Clinvar id is 1232055.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.1549-68C>T		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.1549-68C>T		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.0461 AC: 6727 AN: 145888 Hom.: 218 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.00446

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.0950

Gnomad FIN AF: 0.0238

Gnomad MID AF: 0.0428

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0433

GnomAD4 exome AF: 0.0449 AC: 41448 AN: 923722 Hom.: 1478 AF XY: 0.0464 AC XY: 22195 AN XY: 478826

Gnomad4 AFR exome AF: 0.0478

Gnomad4 AMR exome AF: 0.0330

Gnomad4 ASJ exome AF: 0.0914

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.0832

Gnomad4 FIN exome AF: 0.0237

Gnomad4 NFE exome AF: 0.0330

Gnomad4 OTH exome AF: 0.0512

GnomAD4 genome AF: 0.0461 AC: 6733 AN: 146006 Hom.: 220 Cov.: 32 AF XY: 0.0470 AC XY: 3335 AN XY: 70930

Gnomad4 AFR AF: 0.0524

Gnomad4 AMR AF: 0.0325

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.0947

Gnomad4 FIN AF: 0.0238

Gnomad4 NFE AF: 0.0332

Gnomad4 OTH AF: 0.0443

Alfa AF: 0.0379 Hom.: 34

Bravo AF: 0.0461

Asia WGS AF: 0.114 AC: 394 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.5
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2242208; hg19: chr5-180049907;