rs34117331

Positions:

• chr5-180629986-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_182925.5(FLT4):​c.633A>G​(p.Gly211=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,612,830 control chromosomes in the GnomAD database, including 295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (135 hom., cov: 33)
  • Exomes 𝑓: 0.0039 (160 hom.)
• Consequence: FLT4 NM_182925.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.66

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-180629986-T-C is Benign according to our data. Variant chr5-180629986-T-C is described in ClinVar as [Benign]. Clinvar id is 263067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180629986-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.633A>G	p.Gly211=	synonymous_variant	5/30	ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.633A>G	p.Gly211=	synonymous_variant	5/30	1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3469 AN: 152162 Hom.: 133 Cov.: 33

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0211

GnomAD3 exomes AF: 0.00921 AC: 2301 AN: 249906 Hom.: 61 AF XY: 0.00863 AC XY: 1171 AN XY: 135646

Gnomad AFR exome AF: 0.0781

Gnomad AMR exome AF: 0.00414

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0278

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.00459

GnomAD4 exome AF: 0.00393 AC: 5737 AN: 1460550 Hom.: 160 Cov.: 38 AF XY: 0.00432 AC XY: 3142 AN XY: 726554

Gnomad4 AFR exome AF: 0.0760

Gnomad4 AMR exome AF: 0.00456

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0280

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000944

Gnomad4 OTH exome AF: 0.00742

GnomAD4 genome AF: 0.0229 AC: 3480 AN: 152280 Hom.: 135 Cov.: 33 AF XY: 0.0224 AC XY: 1671 AN XY: 74446

Gnomad4 AFR AF: 0.0738

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0292

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0112 Hom.: 22

Bravo AF: 0.0255

Asia WGS AF: 0.0180 AC: 62 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Sep 13, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.44

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: rs34117331; hg19: chr5-180056986;