Variant 4-176687621-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005429.5(VEGFC):c.812-101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.677 in 1,228,454 control chromosomes in the GnomAD database, including 286,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.59 ( 28364 hom., cov: 33)

Exomes 𝑓: 0.69 ( 258585 hom. )

Consequence

VEGFC
NM_005429.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.767

Variant links:

Genes affected

VEGFC (HGNC:12682): (vascular endothelial growth factor C) The protein encoded by this gene is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family. The encoded protein promotes angiogenesis and endothelial cell growth, and can also affect the permeability of blood vessels. The proprotein is further cleaved into a fully processed form that can bind and activate VEGFR-2 and VEGFR-3 receptors. [provided by RefSeq, Apr 2014]

VEGFC links:

HAFML (HGNC:56694): (HuR (ELAVL1) associated fibroblast migratory lncRNA)

HAFML links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 4-176687621-T-C is Benign according to our data. Variant chr4-176687621-T-C is described in ClinVar as [Benign]. Clinvar id is 1231039.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEGFC	NM_005429.5 linkuse as main transcript	c.812-101A>G		intron_variant		ENST00000618562.2
HAFML	NR_183975.1 linkuse as main transcript	n.182+17912T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
VEGFC	ENST00000618562.2 linkuse as main transcript	c.812-101A>G	intron_variant	1	NM_005429.5	P1
HAFML	ENST00000509194.1 linkuse as main transcript	n.89+17912T>C	intron_variant, non_coding_transcript_variant	3
HAFML	ENST00000504017.5 linkuse as main transcript	n.140+7871T>C	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.586

AC:

89077

AN:

151962

Hom.:

28374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.711

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.675

Gnomad EAS

AF:

0.706

Gnomad SAS

AF:

0.738

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.617

Gnomad NFE

AF:

0.696

Gnomad OTH

AF:

0.600

GnomAD4 exome

AF:

0.689

AC:

742022

AN:

1076374

Hom.:

258585

Cov.:

AF XY:

0.691

AC XY:

366748

AN XY:

530442

show subpopulations

Gnomad4 AFR exome

AF:

0.311

Gnomad4 AMR exome

AF:

0.574

Gnomad4 ASJ exome

AF:

0.673

Gnomad4 EAS exome

AF:

0.701

Gnomad4 SAS exome

AF:

0.735

Gnomad4 FIN exome

AF:

0.727

Gnomad4 NFE exome

AF:

0.699

Gnomad4 OTH exome

AF:

0.668

GnomAD4 genome

AF:

0.586

AC:

89089

AN:

152080

Hom.:

28364

Cov.:

AF XY:

0.595

AC XY:

44255

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.321

Gnomad4 AMR

AF:

0.583

Gnomad4 ASJ

AF:

0.675

Gnomad4 EAS

AF:

0.706

Gnomad4 SAS

AF:

0.737

Gnomad4 FIN

AF:

0.752

Gnomad4 NFE

AF:

0.696

Gnomad4 OTH

AF:

0.598

Alfa

AF:

0.545

Hom.:

2919

Bravo

AF:

0.559

Asia WGS

AF:

0.700

AC:

2432

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.8

DANN

Benign

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over