rs2242215

chr5-180621035-T-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.2168-28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 1,610,814 control chromosomes in the GnomAD database, including 4,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (330 hom., cov: 34)
  • Exomes 𝑓: 0.064 (3713 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.443

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=-0.88).
• BP6: Variant 5-180621035-T-C is Benign according to our data. Variant chr5-180621035-T-C is described in ClinVar as [Benign]. Clinvar id is 263033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.2168-28A>G		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.2168-28A>G		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.0586 AC: 8905 AN: 152028 Hom.: 327 Cov.: 34

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0381

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0570

Gnomad OTH AF: 0.0547

GnomAD3 exomes AF: 0.0735 AC: 18119 AN: 246478 Hom.: 921 AF XY: 0.0778 AC XY: 10445 AN XY: 134306

Gnomad AFR exome AF: 0.0444

Gnomad AMR exome AF: 0.0390

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.185

Gnomad SAS exome AF: 0.134

Gnomad FIN exome AF: 0.0372

Gnomad NFE exome AF: 0.0572

Gnomad OTH exome AF: 0.0710

GnomAD4 exome AF: 0.0639 AC: 93197 AN: 1458668 Hom.: 3713 Cov.: 43 AF XY: 0.0663 AC XY: 48074 AN XY: 725332

Gnomad4 AFR exome AF: 0.0471

Gnomad4 AMR exome AF: 0.0407

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.0369

Gnomad4 NFE exome AF: 0.0554

Gnomad4 OTH exome AF: 0.0703

GnomAD4 genome AF: 0.0586 AC: 8914 AN: 152146 Hom.: 330 Cov.: 34 AF XY: 0.0591 AC XY: 4396 AN XY: 74380

Gnomad4 AFR AF: 0.0459

Gnomad4 AMR AF: 0.0380

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0381

Gnomad4 NFE AF: 0.0570

Gnomad4 OTH AF: 0.0551

Alfa AF: 0.0640 Hom.: 70

Bravo AF: 0.0585

Asia WGS AF: 0.133 AC: 465 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

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.9
Dann	Benign	0.32
La Branchor		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2242215; hg19: chr5-180048035; COSMIC: COSV56099269; COSMIC: COSV56099269;