rs383985

chr5-180628862-T-Cchr5-180628862-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+20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 1,537,158 control chromosomes in the GnomAD database, including 5,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (482 hom., cov: 31)
  • Exomes 𝑓: 0.079 (4968 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.07

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=-0.98).
• BP6: Variant 5-180628862-T-C is Benign according to our data. Variant chr5-180628862-T-C is described in ClinVar as [Benign]. Clinvar id is 263018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180628862-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.1103+20A>G		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.1103+20A>G		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.0675 AC: 10221 AN: 151418 Hom.: 482 Cov.: 31

Gnomad AFR AF: 0.0166

Gnomad AMI AF: 0.00881

Gnomad AMR AF: 0.0472

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0370

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0353

Gnomad NFE AF: 0.0873

Gnomad OTH AF: 0.0541

GnomAD3 exomes AF: 0.0728 AC: 16453 AN: 226054 Hom.: 775 AF XY: 0.0729 AC XY: 9058 AN XY: 124270

Gnomad AFR exome AF: 0.0177

Gnomad AMR exome AF: 0.0314

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.122

Gnomad SAS exome AF: 0.0400

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.0807

Gnomad OTH exome AF: 0.0754

GnomAD4 exome AF: 0.0793 AC: 109917 AN: 1385626 Hom.: 4968 Cov.: 23 AF XY: 0.0788 AC XY: 54509 AN XY: 692172

Gnomad4 AFR exome AF: 0.0143

Gnomad4 AMR exome AF: 0.0338

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.0396

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.0814

Gnomad4 OTH exome AF: 0.0781

GnomAD4 genome AF: 0.0674 AC: 10219 AN: 151532 Hom.: 482 Cov.: 31 AF XY: 0.0680 AC XY: 5035 AN XY: 74024

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.0471

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0374

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.0873

Gnomad4 OTH AF: 0.0559

Alfa AF: 0.0988 Hom.: 1932

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 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.51
Dann	Benign	0.10

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: rs383985; hg19: chr5-180055862; COSMIC: COSV56101064; COSMIC: COSV56101064;