4-176687621-T-C

Position:

• chr4-176687621-T-C

Variant summary

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

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.767

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=-0.83).
• 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_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.812-101A>G		intron_variant		ENST00000618562.2	NP_005420.1
HAFML	NR_183975.1	n.182+17912T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEGFC	ENST00000618562.2	c.812-101A>G		intron_variant		1	NM_005429.5	ENSP00000480043	P1
HAFML	ENST00000509194.1	n.89+17912T>C		intron_variant, non_coding_transcript_variant		3
HAFML	ENST00000504017.5	n.140+7871T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89077 AN: 151962 Hom.: 28374 Cov.: 33

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.: 14 AF XY: 0.691 AC XY: 366748 AN XY: 530442

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.: 33 AF XY: 0.595 AC XY: 44255 AN XY: 74354

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Other links and lift over

dbSNP: rs4604006; hg19: chr4-177608775;