rs2242216

Positions:

• chr5-180614491-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182925.5(FLT4):​c.3220-312G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,926 control chromosomes in the GnomAD database, including 12,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (12348 hom., cov: 31)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-180614491-C-T is Benign according to our data. Variant chr5-180614491-C-T is described in ClinVar as [Benign]. Clinvar id is 1235762.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.3220-312G>A		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.3220-312G>A		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57636 AN: 151808 Hom.: 12354 Cov.: 31

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.379 AC: 57642 AN: 151926 Hom.: 12348 Cov.: 31 AF XY: 0.383 AC XY: 28417 AN XY: 74240

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.393

Alfa AF: 0.434 Hom.: 3530

Bravo AF: 0.361

Asia WGS AF: 0.381 AC: 1325 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.90
CADD	Benign	0.20
DANN	Benign	0.47

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: rs2242216; hg19: chr5-180041491;