rs2242219

Variant names:

• chr5-180609871-C-G
• rs2242219
• NM_182925.5:c.3807+34G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-180609871-C-G
• chr5-180609871-C-A
• chr5-180609871-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182925.5(FLT4):​c.3807+34G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 1,613,224 control chromosomes in the GnomAD database, including 3,693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (295 hom., cov: 33)
  • Exomes 𝑓: 0.062 (3398 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.306
• Publications: 7 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):

• congenital heart defects, multiple types, 7

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• lymphatic malformation 1

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

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-180609871-C-G is Benign according to our data. Variant chr5-180609871-C-G is described in ClinVar as Benign. ClinVar VariationId is 263052.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 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.3807+34G>C		intron	N/A	NP_891555.2	P35916-2
	FLT4	NM_001354989.2		c.3807+34G>C		intron	N/A	NP_001341918.1	E9PD35
	FLT4	NM_002020.5		c.3807+34G>C		intron	N/A	NP_002011.2	P35916-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT4	ENST00000261937.11	TSL:1 MANE Select	c.3807+34G>C		intron	N/A	ENSP00000261937.6	P35916-2
	FLT4	ENST00000502649.5	TSL:1	c.3807+34G>C		intron	N/A	ENSP00000426057.1	E9PD35
	FLT4	ENST00000393347.7	TSL:1	c.3807+34G>C		intron	N/A	ENSP00000377016.3	P35916-1

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 8536 AN: 152136 Hom.: 295 Cov.: 33

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0373

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.0579

GnomAD2 exomes AF: 0.0682 AC: 17013 AN: 249578 AF XY: 0.0729

Gnomad AFR exome AF: 0.0442

Gnomad AMR exome AF: 0.0384

Gnomad ASJ exome AF: 0.110

Gnomad EAS exome AF: 0.133

Gnomad FIN exome AF: 0.0279

Gnomad NFE exome AF: 0.0557

Gnomad OTH exome AF: 0.0687

GnomAD4 exome AF: 0.0615 AC: 89853 AN: 1460970 Hom.: 3398 Cov.: 31 AF XY: 0.0640 AC XY: 46528 AN XY: 726794

African (AFR) AF: 0.0486 AC: 1624 AN: 33444

American (AMR) AF: 0.0401 AC: 1790 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2835 AN: 26114

East Asian (EAS) AF: 0.150 AC: 5962 AN: 39682

South Asian (SAS) AF: 0.133 AC: 11468 AN: 86214

European-Finnish (FIN) AF: 0.0272 AC: 1451 AN: 53344

Middle Eastern (MID) AF: 0.0847 AC: 484 AN: 5716

European-Non Finnish (NFE) AF: 0.0542 AC: 60188 AN: 1111432

Other (OTH) AF: 0.0671 AC: 4051 AN: 60332

GnomAD4 genome AF: 0.0560 AC: 8533 AN: 152254 Hom.: 295 Cov.: 33 AF XY: 0.0562 AC XY: 4188 AN XY: 74454

African (AFR) AF: 0.0465 AC: 1930 AN: 41550

American (AMR) AF: 0.0372 AC: 569 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3472

East Asian (EAS) AF: 0.138 AC: 716 AN: 5172

South Asian (SAS) AF: 0.136 AC: 655 AN: 4822

European-Finnish (FIN) AF: 0.0279 AC: 296 AN: 10616

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0561 AC: 3814 AN: 67996

Other (OTH) AF: 0.0587 AC: 124 AN: 2112

Alfa AF: 0.0356 Hom.: 39

Bravo AF: 0.0558

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.42
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2242219; hg19: chr5-180036871; COSMIC: COSV56099233; COSMIC: COSV56099233;