chr5-180607823-T-C

Position:

• chr5-180607823-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182925.5(FLT4):​c.3893+1145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 456,178 control chromosomes in the GnomAD database, including 22,723 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (7124 hom., cov: 31)
  • Exomes 𝑓: 0.31 (15599 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.83

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLT4	NM_182925.5	c.3893+1145A>G		intron_variant		ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.3893+1145A>G		intron_variant		1	NM_182925.5	ENSP00000261937	P1
FLT4	ENST00000502603.5	n.593+1145A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45898 AN: 151862 Hom.: 7124 Cov.: 31

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.310

GnomAD4 exome AF: 0.313 AC: 95247 AN: 304198 Hom.: 15599 AF XY: 0.317 AC XY: 49683 AN XY: 156606

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.379

Gnomad4 EAS exome AF: 0.330

Gnomad4 SAS exome AF: 0.348

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.316

GnomAD4 genome AF: 0.302 AC: 45907 AN: 151980 Hom.: 7124 Cov.: 31 AF XY: 0.300 AC XY: 22291 AN XY: 74296

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.310

Alfa AF: 0.311 Hom.: 922

Bravo AF: 0.299

Asia WGS AF: 0.326 AC: 1137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.21
DANN	Benign	0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1049095; hg19: chr5-180034823;