rs56401579

chr5-180626090-G-A

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.1258+21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 1,612,668 control chromosomes in the GnomAD database, including 1,981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (192 hom., cov: 33)
  • Exomes 𝑓: 0.040 (1789 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.627

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=-0.91).
• BP6: Variant 5-180626090-G-A is Benign according to our data. Variant chr5-180626090-G-A is described in ClinVar as [Benign]. Clinvar id is 263022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.1258+21C>T		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.1258+21C>T		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.0416 AC: 6325 AN: 152110 Hom.: 190 Cov.: 33

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0293

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.0889

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.0393

GnomAD3 exomes AF: 0.0521 AC: 12955 AN: 248746 Hom.: 603 AF XY: 0.0538 AC XY: 7267 AN XY: 135172

Gnomad AFR exome AF: 0.0407

Gnomad AMR exome AF: 0.0310

Gnomad ASJ exome AF: 0.0919

Gnomad EAS exome AF: 0.182

Gnomad SAS exome AF: 0.0848

Gnomad FIN exome AF: 0.0214

Gnomad NFE exome AF: 0.0322

Gnomad OTH exome AF: 0.0525

GnomAD4 exome AF: 0.0402 AC: 58704 AN: 1460440 Hom.: 1789 Cov.: 34 AF XY: 0.0414 AC XY: 30057 AN XY: 726510

Gnomad4 AFR exome AF: 0.0398

Gnomad4 AMR exome AF: 0.0318

Gnomad4 ASJ exome AF: 0.0902

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.0831

Gnomad4 FIN exome AF: 0.0229

Gnomad4 NFE exome AF: 0.0314

Gnomad4 OTH exome AF: 0.0489

GnomAD4 genome AF: 0.0416 AC: 6331 AN: 152228 Hom.: 192 Cov.: 33 AF XY: 0.0423 AC XY: 3146 AN XY: 74414

Gnomad4 AFR AF: 0.0419

Gnomad4 AMR AF: 0.0293

Gnomad4 ASJ AF: 0.0931

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.0883

Gnomad4 FIN AF: 0.0221

Gnomad4 NFE AF: 0.0311

Gnomad4 OTH AF: 0.0403

Alfa AF: 0.0431 Hom.: 34

Bravo AF: 0.0434

Asia WGS AF: 0.112 AC: 389 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	-0.91
Cadd	Benign	0.34
Dann	Benign	0.61

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: rs56401579; hg19: chr5-180053090; COSMIC: COSV56099311; COSMIC: COSV56099311;