chr5-180608347-C-T

Position:

• chr5-180608347-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.3893+621G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 700,534 control chromosomes in the GnomAD database, including 24,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (4219 hom., cov: 32)
  • Exomes 𝑓: 0.27 (20160 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.969

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=-1.0).
• BP6: Variant 5-180608347-C-T is Benign according to our data. Variant chr5-180608347-C-T is described in ClinVar as [Benign]. Clinvar id is 1279900.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.3893+621G>A		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.3893+621G>A		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33590 AN: 151978 Hom.: 4223 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.266 AC: 145874 AN: 548436 Hom.: 20160 AF XY: 0.274 AC XY: 81445 AN XY: 296980

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.261

GnomAD4 genome AF: 0.221 AC: 33578 AN: 152098 Hom.: 4219 Cov.: 32 AF XY: 0.222 AC XY: 16487 AN XY: 74340

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.239

Alfa AF: 0.245 Hom.: 611

Bravo AF: 0.211

Asia WGS AF: 0.248 AC: 864 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 21, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.55

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: rs2387212; hg19: chr5-180035347; COSMIC: COSV56099223; COSMIC: COSV56099223;