4-176688049-G-A

Position:

• chr4-176688049-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000618562.2(VEGFC):​c.705-122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 538,242 control chromosomes in the GnomAD database, including 118,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (28326 hom., cov: 32)
  • Exomes 𝑓: 0.68 (90043 hom.)
• Consequence: VEGFC ENST00000618562.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.503

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]

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

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-176688049-G-A is Benign according to our data. Variant chr4-176688049-G-A is described in ClinVar as [Benign]. Clinvar id is 1250186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
VEGFC	NM_005429.5	c.705-122C>T		intron_variant		ENST00000618562.2	NP_005420.1
HAFML	NR_183975.1	n.183-17854G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEGFC	ENST00000618562.2	c.705-122C>T		intron_variant		1	NM_005429.5	ENSP00000480043	P1
HAFML	ENST00000509194.1	n.90-17854G>A		intron_variant, non_coding_transcript_variant		3
HAFML	ENST00000504017.5	n.140+8299G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89016 AN: 151888 Hom.: 28336 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.678 AC: 261926 AN: 386236 Hom.: 90043 AF XY: 0.681 AC XY: 136314 AN XY: 200274

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.561

Gnomad4 ASJ exome AF: 0.666

Gnomad4 EAS exome AF: 0.686

Gnomad4 SAS exome AF: 0.708

Gnomad4 FIN exome AF: 0.728

Gnomad4 NFE exome AF: 0.691

Gnomad4 OTH exome AF: 0.647

GnomAD4 genome AF: 0.586 AC: 89028 AN: 152006 Hom.: 28326 Cov.: 32 AF XY: 0.595 AC XY: 44201 AN XY: 74292

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.696

Gnomad4 OTH AF: 0.599

Alfa AF: 0.616 Hom.: 3763

Bravo AF: 0.559

Asia WGS AF: 0.699 AC: 2422 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.90
CADD	Benign	5.5
DANN	Benign	0.47

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: rs13136065; hg19: chr4-177609203;