rs2242217

chr5-180613918-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.3331+150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 705,214 control chromosomes in the GnomAD database, including 71,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (13236 hom., cov: 33)
  • Exomes 𝑓: 0.45 (57781 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0770

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 5-180613918-G-A is Benign according to our data. Variant chr5-180613918-G-A is described in ClinVar as [Benign]. Clinvar id is 1260711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.3331+150C>T		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.3331+150C>T		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61622 AN: 151918 Hom.: 13241 Cov.: 33

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.417

GnomAD4 exome AF: 0.452 AC: 249858 AN: 553178 Hom.: 57781 Cov.: 5 AF XY: 0.453 AC XY: 135308 AN XY: 298572

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.416

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.514

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.449

GnomAD4 genome AF: 0.405 AC: 61627 AN: 152036 Hom.: 13236 Cov.: 33 AF XY: 0.408 AC XY: 30336 AN XY: 74322

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.413

Alfa AF: 0.461 Hom.: 18950

Bravo AF: 0.391

Asia WGS AF: 0.384 AC: 1334 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	10
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2242217; hg19: chr5-180040918; COSMIC: COSV56118998; COSMIC: COSV56118998;