5-180616330-C-G

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.3219+37G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 1,613,180 control chromosomes in the GnomAD database, including 2,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (161 hom., cov: 31)
  • Exomes 𝑓: 0.048 (1991 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.69

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=-1.01).
• BP6: Variant 5-180616330-C-G is Benign according to our data. Variant chr5-180616330-C-G is described in ClinVar as [Benign]. Clinvar id is 263045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.3219+37G>C		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.3219+37G>C		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5578 AN: 152230 Hom.: 161 Cov.: 31

Gnomad AFR AF: 0.00965

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0861

Gnomad EAS AF: 0.0869

Gnomad SAS AF: 0.0267

Gnomad FIN AF: 0.0393

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0484

Gnomad OTH AF: 0.0353

GnomAD3 exomes AF: 0.0428 AC: 10736 AN: 250730 Hom.: 331 AF XY: 0.0431 AC XY: 5850 AN XY: 135672

Gnomad AFR exome AF: 0.00968

Gnomad AMR exome AF: 0.0237

Gnomad ASJ exome AF: 0.0880

Gnomad EAS exome AF: 0.0880

Gnomad SAS exome AF: 0.0290

Gnomad FIN exome AF: 0.0368

Gnomad NFE exome AF: 0.0469

Gnomad OTH exome AF: 0.0442

GnomAD4 exome AF: 0.0483 AC: 70518 AN: 1460832 Hom.: 1991 Cov.: 31 AF XY: 0.0478 AC XY: 34774 AN XY: 726790

Gnomad4 AFR exome AF: 0.00768

Gnomad4 AMR exome AF: 0.0250

Gnomad4 ASJ exome AF: 0.0822

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.0283

Gnomad4 FIN exome AF: 0.0378

Gnomad4 NFE exome AF: 0.0498

Gnomad4 OTH exome AF: 0.0480

GnomAD4 genome AF: 0.0366 AC: 5580 AN: 152348 Hom.: 161 Cov.: 31 AF XY: 0.0351 AC XY: 2612 AN XY: 74494

Gnomad4 AFR AF: 0.00959

Gnomad4 AMR AF: 0.0325

Gnomad4 ASJ AF: 0.0861

Gnomad4 EAS AF: 0.0871

Gnomad4 SAS AF: 0.0269

Gnomad4 FIN AF: 0.0393

Gnomad4 NFE AF: 0.0484

Gnomad4 OTH AF: 0.0373

Alfa AF: 0.0303 Hom.: 27

Bravo AF: 0.0357

Asia WGS AF: 0.0530 AC: 187 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

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.0050
Dann	Benign	0.33

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: rs55657009; hg19: chr5-180043330; COSMIC: COSV56100306; COSMIC: COSV56100306;