rs75361132

Variant names:

• chr5-180628849-T-C
• rs75361132
• NM_182925.5:c.1103+33A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-180628849-T-C
• chr5-180628849-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_182925.5(FLT4):​c.1103+33A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,421,458 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.856
• Publications: 5 publications found

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]

FLT4 Gene-Disease associations (from GenCC):

• lymphatic malformation 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• capillary infantile hemangioma

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• congenital heart defects, multiple types, 7

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• lymphatic malformation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• tetralogy of fallot

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182925.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	NM_182925.5	MANE Select	c.1103+33A>G		intron	N/A	NP_891555.2
	FLT4	NM_001354989.2		c.1103+33A>G		intron	N/A	NP_001341918.1
	FLT4	NM_002020.5		c.1103+33A>G		intron	N/A	NP_002011.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	ENST00000261937.11	TSL:1 MANE Select	c.1103+33A>G		intron	N/A	ENSP00000261937.6
	FLT4	ENST00000502649.5	TSL:1	c.1103+33A>G		intron	N/A	ENSP00000426057.1
	FLT4	ENST00000393347.7	TSL:1	c.1103+33A>G		intron	N/A	ENSP00000377016.3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151970 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.88e-7 AC: 1 AN: 1269488 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 636808

African (AFR) AF: 0.00 AC: 0 AN: 30384

American (AMR) AF: 0.00 AC: 0 AN: 43480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22588

East Asian (EAS) AF: 0.00 AC: 0 AN: 38584

South Asian (SAS) AF: 0.00 AC: 0 AN: 77016

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4836

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 955998

Other (OTH) AF: 0.0000185 AC: 1 AN: 54054

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151970 Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2 AN XY: 74206

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.000131 AC: 2 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5136

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 94

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	19
DANN	Benign	0.67
PhyloP100		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.34		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.34		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs75361132; hg19: chr5-180055849;