rs144453562

Positions:

• chr5-180625831-TGGCTGTGCAGGGGACCTGA-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_182925.5(FLT4):​c.1421+19_1421+37del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,598,372 control chromosomes in the GnomAD database, including 2,172 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (583 hom., cov: 32)
  • Exomes 𝑓: 0.024 (1589 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00

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 -16 ACMG points.

• BP6: Variant 5-180625831-TGGCTGTGCAGGGGACCTGA-T is Benign according to our data. Variant chr5-180625831-TGGCTGTGCAGGGGACCTGA-T is described in ClinVar as [Benign]. Clinvar id is 263025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180625831-TGGCTGTGCAGGGGACCTGA-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.1421+19_1421+37del		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.1421+19_1421+37del		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9134 AN: 152052 Hom.: 576 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.0411

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.0521

GnomAD3 exomes AF: 0.0479 AC: 11413 AN: 238210 Hom.: 673 AF XY: 0.0432 AC XY: 5624 AN XY: 130112

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.0579

Gnomad ASJ exome AF: 0.0471

Gnomad EAS exome AF: 0.218

Gnomad SAS exome AF: 0.0243

Gnomad FIN exome AF: 0.0362

Gnomad NFE exome AF: 0.0137

Gnomad OTH exome AF: 0.0389

GnomAD4 exome AF: 0.0244 AC: 35344 AN: 1446200 Hom.: 1589 AF XY: 0.0241 AC XY: 17338 AN XY: 720018

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.0551

Gnomad4 ASJ exome AF: 0.0468

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.0261

Gnomad4 FIN exome AF: 0.0366

Gnomad4 NFE exome AF: 0.0111

Gnomad4 OTH exome AF: 0.0376

GnomAD4 genome AF: 0.0604 AC: 9185 AN: 152172 Hom.: 583 Cov.: 32 AF XY: 0.0623 AC XY: 4636 AN XY: 74406

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0391

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.0340

Gnomad4 FIN AF: 0.0411

Gnomad4 NFE AF: 0.0119

Gnomad4 OTH AF: 0.0591

Alfa AF: 0.0381 Hom.: 44

Bravo AF: 0.0676

Asia WGS AF: 0.137 AC: 473 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs144453562; hg19: chr5-180052831;