rs56401579

Variant names:

• chr5-180626090-G-A
• rs56401579
• NM_182925.5:c.1258+21C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-180626090-G-A
• chr5-180626090-G-C
• chr5-180626090-G-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.1258+21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0403 in 1,612,668 control chromosomes in the GnomAD database, including 1,981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (192 hom., cov: 33)
  • Exomes 𝑓: 0.040 (1789 hom.)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.627
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-180626090-G-A is Benign according to our data. Variant chr5-180626090-G-A is described in ClinVar as Benign. ClinVar VariationId is 263022.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5	c.1258+21C>T		intron_variant	Intron 9 of 29	ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.1258+21C>T		intron_variant	Intron 9 of 29	1	NM_182925.5	ENSP00000261937.6

Frequencies

GnomAD3 genomes AF: 0.0416 AC: 6325 AN: 152110 Hom.: 190 Cov.: 33

Gnomad AFR AF: 0.0418

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0293

Gnomad ASJ AF: 0.0931

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.0889

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0311

Gnomad OTH AF: 0.0393

GnomAD2 exomes AF: 0.0521 AC: 12955 AN: 248746 AF XY: 0.0538

Gnomad AFR exome AF: 0.0407

Gnomad AMR exome AF: 0.0310

Gnomad ASJ exome AF: 0.0919

Gnomad EAS exome AF: 0.182

Gnomad FIN exome AF: 0.0214

Gnomad NFE exome AF: 0.0322

Gnomad OTH exome AF: 0.0525

GnomAD4 exome AF: 0.0402 AC: 58704 AN: 1460440 Hom.: 1789 Cov.: 34 AF XY: 0.0414 AC XY: 30057 AN XY: 726510

African (AFR) AF: 0.0398 AC: 1334 AN: 33480

American (AMR) AF: 0.0318 AC: 1420 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0902 AC: 2358 AN: 26132

East Asian (EAS) AF: 0.177 AC: 7046 AN: 39700

South Asian (SAS) AF: 0.0831 AC: 7167 AN: 86256

European-Finnish (FIN) AF: 0.0229 AC: 1192 AN: 52028

Middle Eastern (MID) AF: 0.0532 AC: 307 AN: 5768

European-Non Finnish (NFE) AF: 0.0314 AC: 34927 AN: 1111978

Other (OTH) AF: 0.0489 AC: 2953 AN: 60378

GnomAD4 genome AF: 0.0416 AC: 6331 AN: 152228 Hom.: 192 Cov.: 33 AF XY: 0.0423 AC XY: 3146 AN XY: 74414

African (AFR) AF: 0.0419 AC: 1740 AN: 41548

American (AMR) AF: 0.0293 AC: 448 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 323 AN: 3470

East Asian (EAS) AF: 0.182 AC: 943 AN: 5172

South Asian (SAS) AF: 0.0883 AC: 426 AN: 4824

European-Finnish (FIN) AF: 0.0221 AC: 234 AN: 10604

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0311 AC: 2115 AN: 67996

Other (OTH) AF: 0.0403 AC: 85 AN: 2110

Alfa AF: 0.0431 Hom.: 34

Bravo AF: 0.0434

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.61
PhyloP100		-0.63
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: rs56401579; hg19: chr5-180053090; COSMIC: COSV56099311; COSMIC: COSV56099311;