chr5-180623148-T-C

Variant names:

• chr5-180623148-T-C
• rs307827
• NM_182925.5:c.1549-309A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182925.5(FLT4):​c.1549-309A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,094 control chromosomes in the GnomAD database, including 43,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.74 (43780 hom., cov: 32)
• Consequence: FLT4 NM_182925.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-180623148-T-C is Benign according to our data. Variant chr5-180623148-T-C is described in ClinVar as [Benign]. Clinvar id is 1290906.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLT4	NM_182925.5	c.1549-309A>G		intron_variant	Intron 11 of 29	ENST00000261937.11	NP_891555.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLT4	ENST00000261937.11	c.1549-309A>G		intron_variant	Intron 11 of 29	1	NM_182925.5	ENSP00000261937.6

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112747 AN: 151976 Hom.: 43775 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.867

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.742 AC: 112779 AN: 152094 Hom.: 43780 Cov.: 32 AF XY: 0.743 AC XY: 55280 AN XY: 74360

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.812

Gnomad4 FIN AF: 0.867

Gnomad4 NFE AF: 0.855

Gnomad4 OTH AF: 0.747

Alfa AF: 0.808 Hom.: 7948

Bravo AF: 0.721

Asia WGS AF: 0.690 AC: 2403 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.16
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs307827; hg19: chr5-180050148;