rs3797104

Variant names:

• chr5-180624987-T-C
• rs3797104
• NM_182925.5:c.1421+882A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182925.5(FLT4):​c.1421+882A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,216 control chromosomes in the GnomAD database, including 2,137 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 0.16 (2137 hom., cov: 33)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	NM_182925.5	MANE Select	c.1421+882A>G		intron	N/A	NP_891555.2
	FLT4	NM_001354989.2		c.1421+882A>G		intron	N/A	NP_001341918.1
	FLT4	NM_002020.5		c.1421+882A>G		intron	N/A	NP_002011.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	ENST00000261937.11	TSL:1 MANE Select	c.1421+882A>G		intron	N/A	ENSP00000261937.6
	FLT4	ENST00000502649.5	TSL:1	c.1421+882A>G		intron	N/A	ENSP00000426057.1
	FLT4	ENST00000393347.7	TSL:1	c.1421+882A>G		intron	N/A	ENSP00000377016.3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23735 AN: 152096 Hom.: 2121 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.156 AC: 23797 AN: 152216 Hom.: 2137 Cov.: 33 AF XY: 0.156 AC XY: 11635 AN XY: 74414

African (AFR) AF: 0.244 AC: 10144 AN: 41524

American (AMR) AF: 0.128 AC: 1960 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3472

East Asian (EAS) AF: 0.217 AC: 1119 AN: 5156

South Asian (SAS) AF: 0.110 AC: 529 AN: 4818

European-Finnish (FIN) AF: 0.108 AC: 1143 AN: 10614

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 7993 AN: 68016

Other (OTH) AF: 0.172 AC: 364 AN: 2112

Alfa AF: 0.130 Hom.: 2331

Bravo AF: 0.166

Asia WGS AF: 0.186 AC: 647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.45
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3797104; hg19: chr5-180051987; COSMIC: COSV56102583; COSMIC: COSV56102583;