5-180628849-T-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.1103+33A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0335 in 1,421,056 control chromosomes in the GnomAD database, including 4,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.046 (591 hom., cov: 33)
  • Exomes 𝑓: 0.032 (3848 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.856

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 5-180628849-T-G is Benign according to our data. Variant chr5-180628849-T-G is described in ClinVar as [Benign]. Clinvar id is 263019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.1103+33A>C		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.1103+33A>C		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7036 AN: 151944 Hom.: 584 Cov.: 33

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.0445

Gnomad MID AF: 0.0414

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0459

GnomAD3 exomes AF: 0.0741 AC: 15573 AN: 210076 Hom.: 2039 AF XY: 0.0699 AC XY: 7994 AN XY: 114338

Gnomad AFR exome AF: 0.0620

Gnomad AMR exome AF: 0.0613

Gnomad ASJ exome AF: 0.0627

Gnomad EAS exome AF: 0.453

Gnomad SAS exome AF: 0.0643

Gnomad FIN exome AF: 0.0596

Gnomad NFE exome AF: 0.0163

Gnomad OTH exome AF: 0.0515

GnomAD4 exome AF: 0.0320 AC: 40553 AN: 1268994 Hom.: 3848 Cov.: 20 AF XY: 0.0326 AC XY: 20766 AN XY: 636564

Gnomad4 AFR exome AF: 0.0565

Gnomad4 AMR exome AF: 0.0560

Gnomad4 ASJ exome AF: 0.0492

Gnomad4 EAS exome AF: 0.408

Gnomad4 SAS exome AF: 0.0578

Gnomad4 FIN exome AF: 0.0441

Gnomad4 NFE exome AF: 0.0111

Gnomad4 OTH exome AF: 0.0457

GnomAD4 genome AF: 0.0465 AC: 7068 AN: 152062 Hom.: 591 Cov.: 33 AF XY: 0.0502 AC XY: 3728 AN XY: 74320

Gnomad4 AFR AF: 0.0596

Gnomad4 AMR AF: 0.0334

Gnomad4 ASJ AF: 0.0424

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.0679

Gnomad4 FIN AF: 0.0445

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0176 Hom.: 22

Bravo AF: 0.0509

Asia WGS AF: 0.214 AC: 742 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	12
Dann	Benign	0.25

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: rs75361132; hg19: chr5-180055849; COSMIC: COSV56099894; COSMIC: COSV56099894;