5-180628862-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182925.5(FLT4):c.1103+20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,535,060 control chromosomes in the GnomAD database, including 262,661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (25376 hom., cov: 31)
  • Exomes 𝑓: 0.58 (237285 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.07

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 5-180628862-T-G is Benign according to our data. Variant chr5-180628862-T-G is described in ClinVar as [Benign]. Clinvar id is 263017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-180628862-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FLT4	NM_182925.5	c.1103+20A>C		intron_variant		ENST00000261937.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLT4	ENST00000261937.11	c.1103+20A>C		intron_variant		1	NM_182925.5	P1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87092 AN: 151350 Hom.: 25338 Cov.: 31

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.596

GnomAD3 exomes AF: 0.613 AC: 138649 AN: 226054 Hom.: 43103 AF XY: 0.605 AC XY: 75224 AN XY: 124270

Gnomad AFR exome AF: 0.541

Gnomad AMR exome AF: 0.734

Gnomad ASJ exome AF: 0.565

Gnomad EAS exome AF: 0.823

Gnomad SAS exome AF: 0.586

Gnomad FIN exome AF: 0.533

Gnomad NFE exome AF: 0.572

Gnomad OTH exome AF: 0.587

GnomAD4 exome AF: 0.583 AC: 806235 AN: 1383594 Hom.: 237285 Cov.: 23 AF XY: 0.581 AC XY: 401645 AN XY: 691210

Gnomad4 AFR exome AF: 0.542

Gnomad4 AMR exome AF: 0.728

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.788

Gnomad4 SAS exome AF: 0.573

Gnomad4 FIN exome AF: 0.523

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.576 AC: 87178 AN: 151466 Hom.: 25376 Cov.: 31 AF XY: 0.574 AC XY: 42491 AN XY: 73988

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.598

Alfa AF: 0.477 Hom.: 1932

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

-

- -

Congenital heart defects, multiple types, 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Hereditary lymphedema type I Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.2
Dann	Benign	0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs383985; hg19: chr5-180055862;