chr5-180608837-C-T

Position:

• chr5-180608837-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_182925.5(FLT4):​c.3893+131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 793,498 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (6 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.256

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=-0.85).
• BP6: Variant 5-180608837-C-T is Benign according to our data. Variant chr5-180608837-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656151.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0033 (502/152276) while in subpopulation NFE AF= 0.0056 (381/68012). AF 95% confidence interval is 0.00514. There are 0 homozygotes in gnomad4. There are 228 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.3893+131G>A		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.3893+131G>A		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.00330 AC: 502 AN: 152158 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00560

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.00422 AC: 2708 AN: 641222 Hom.: 6 AF XY: 0.00394 AC XY: 1358 AN XY: 345072

Gnomad4 AFR exome AF: 0.00107

Gnomad4 AMR exome AF: 0.000465

Gnomad4 ASJ exome AF: 0.000732

Gnomad4 EAS exome AF: 0.0000289

Gnomad4 SAS exome AF: 0.0000739

Gnomad4 FIN exome AF: 0.00753

Gnomad4 NFE exome AF: 0.00580

Gnomad4 OTH exome AF: 0.00337

GnomAD4 genome AF: 0.00330 AC: 502 AN: 152276 Hom.: 0 Cov.: 33 AF XY: 0.00306 AC XY: 228 AN XY: 74454

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.000523

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00659

Gnomad4 NFE AF: 0.00560

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00303 Hom.: 0

Bravo AF: 0.00288

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

FLT4: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.3
DANN	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs564100331; hg19: chr5-180035837; COSMIC: COSV56124381; COSMIC: COSV56124381;