rs2242213

Positions:

• chr5-180621316-C-G

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.2021-64G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0693 in 1,560,584 control chromosomes in the GnomAD database, including 4,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (428 hom., cov: 33)
  • Exomes 𝑓: 0.070 (3785 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.220

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=-0.82).
• BP6: Variant 5-180621316-C-G is Benign according to our data. Variant chr5-180621316-C-G is described in ClinVar as [Benign]. Clinvar id is 1295068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.2021-64G>C		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.2021-64G>C		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9179 AN: 152056 Hom.: 428 Cov.: 33

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.0381

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.0574

GnomAD4 exome AF: 0.0703 AC: 98943 AN: 1408406 Hom.: 3785 Cov.: 29 AF XY: 0.0704 AC XY: 48991 AN XY: 696056

Gnomad4 AFR exome AF: 0.00965

Gnomad4 AMR exome AF: 0.0945

Gnomad4 ASJ exome AF: 0.0396

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.0658

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.0697

Gnomad4 OTH exome AF: 0.0655

GnomAD4 genome AF: 0.0603 AC: 9179 AN: 152178 Hom.: 428 Cov.: 33 AF XY: 0.0632 AC XY: 4706 AN XY: 74406

Gnomad4 AFR AF: 0.0127

Gnomad4 AMR AF: 0.0833

Gnomad4 ASJ AF: 0.0381

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.0623

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0731

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0756 Hom.: 81

Bravo AF: 0.0560

Asia WGS AF: 0.0870 AC: 301 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.64

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: rs2242213; hg19: chr5-180048316; COSMIC: COSV56102203; COSMIC: COSV56102203;