4-176687721-A-C

Variant summary

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

The NM_005429.5(VEGFC):c.811+100T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,074,762 control chromosomes in the GnomAD database, including 536,167 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 1.0 (75553 hom., cov: 33)
  • Exomes 𝑓: 1.0 (460614 hom.)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.990

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-176687721-A-C is Benign according to our data. Variant chr4-176687721-A-C is described in ClinVar as [Benign]. Clinvar id is 1291631.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEGFC	NM_005429.5	c.811+100T>G		intron_variant		ENST00000618562.2
HAFML	NR_183975.1	n.182+18012A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VEGFC	ENST00000618562.2	c.811+100T>G		intron_variant		1	NM_005429.5	P1
HAFML	ENST00000509194.1	n.89+18012A>C		intron_variant, non_coding_transcript_variant		3
HAFML	ENST00000504017.5	n.140+7971A>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.996 AC: 151585 AN: 152186 Hom.: 75495 Cov.: 33

Gnomad AFR AF: 0.987

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.994

GnomAD4 exome AF: 0.999 AC: 921839 AN: 922458 Hom.: 460614 Cov.: 12 AF XY: 0.999 AC XY: 464877 AN XY: 465178

Gnomad4 AFR exome AF: 0.987

Gnomad4 AMR exome AF: 0.999

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.999

GnomAD4 genome AF: 0.996 AC: 151702 AN: 152304 Hom.: 75553 Cov.: 33 AF XY: 0.996 AC XY: 74201 AN XY: 74480

Gnomad4 AFR AF: 0.987

Gnomad4 AMR AF: 0.999

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.994

Alfa AF: 0.947 Hom.: 3328

Bravo AF: 0.996

Asia WGS AF: 0.999 AC: 3474 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.2
Dann	Benign	0.37

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: rs4529000; hg19: chr4-177608875;