5-180603132-C-T

Position:

• chr5-180603132-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.*60G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,549,076 control chromosomes in the GnomAD database, including 292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (113 hom., cov: 33)
  • Exomes 𝑓: 0.010 (179 hom.)
• Consequence: FLT4 NM_182925.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.238

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=-0.78).
• BP6: Variant 5-180603132-C-T is Benign according to our data. Variant chr5-180603132-C-T is described in ClinVar as [Benign]. Clinvar id is 1274028.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.*60G>A		3_prime_UTR_variant	30/30	ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.*60G>A		3_prime_UTR_variant	30/30	1	NM_182925.5	P1
FLT4	ENST00000502603.5	n.852G>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 3955 AN: 152230 Hom.: 113 Cov.: 33

Gnomad AFR AF: 0.0703

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00641

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00925

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0103 AC: 14384 AN: 1396728 Hom.: 179 Cov.: 26 AF XY: 0.0102 AC XY: 7083 AN XY: 697174

Gnomad4 AFR exome AF: 0.0747

Gnomad4 AMR exome AF: 0.0102

Gnomad4 ASJ exome AF: 0.00838

Gnomad4 EAS exome AF: 0.0000510

Gnomad4 SAS exome AF: 0.00545

Gnomad4 FIN exome AF: 0.00295

Gnomad4 NFE exome AF: 0.00933

Gnomad4 OTH exome AF: 0.0127

GnomAD4 genome AF: 0.0261 AC: 3978 AN: 152348 Hom.: 113 Cov.: 33 AF XY: 0.0258 AC XY: 1922 AN XY: 74506

Gnomad4 AFR AF: 0.0706

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00642

Gnomad4 FIN AF: 0.00292

Gnomad4 NFE AF: 0.00925

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0145 Hom.: 7

Bravo AF: 0.0289

Asia WGS AF: 0.0140 AC: 48 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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.2
DANN	Benign	0.83

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: rs113034305; hg19: chr5-180030132;