rs13359473

chr5-180629044-G-Achr5-180629044-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182925.5(FLT4):c.986-45C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,543,294 control chromosomes in the GnomAD database, including 83,165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6467 hom., cov: 33)
  • Exomes 𝑓: 0.33 (76698 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.831

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 5-180629044-G-A is Benign according to our data. Variant chr5-180629044-G-A is described in ClinVar as [Benign]. Clinvar id is 263072.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.986-45C>T		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.986-45C>T		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41883 AN: 152064 Hom.: 6467 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.0640

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.285

GnomAD3 exomes AF: 0.295 AC: 73033 AN: 247560 Hom.: 11818 AF XY: 0.308 AC XY: 41554 AN XY: 134832

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.300

Gnomad EAS exome AF: 0.0542

Gnomad SAS exome AF: 0.377

Gnomad FIN exome AF: 0.348

Gnomad NFE exome AF: 0.344

Gnomad OTH exome AF: 0.323

GnomAD4 exome AF: 0.327 AC: 454749 AN: 1391112 Hom.: 76698 Cov.: 25 AF XY: 0.330 AC XY: 229948 AN XY: 695876

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.0790

Gnomad4 SAS exome AF: 0.379

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.317

GnomAD4 genome AF: 0.275 AC: 41882 AN: 152182 Hom.: 6467 Cov.: 33 AF XY: 0.279 AC XY: 20740 AN XY: 74418

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.0640

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.282

Alfa AF: 0.245 Hom.: 939

Bravo AF: 0.258

Asia WGS AF: 0.203 AC: 709 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

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	4.9
Dann	Benign	0.39

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: rs13359473; hg19: chr5-180056044; COSMIC: COSV56102210; COSMIC: COSV56102210;