4-176687621-T-A

Variant names:

• chr4-176687621-T-A
• rs4604006
• NM_005429.5:c.812-101A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005429.5(VEGFC):​c.812-101A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• Publications: 28 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005429.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	NM_005429.5	MANE Select	c.812-101A>T		intron	N/A	NP_005420.1
	HAFML	NR_183975.1		n.182+17912T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.812-101A>T		intron	N/A	ENSP00000480043.1
	HAFML	ENST00000504017.6	TSL:2	n.243+7871T>A		intron	N/A
	HAFML	ENST00000509194.2	TSL:3	n.155+17912T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1078542 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 531466

African (AFR) AF: 0.00 AC: 0 AN: 23998

American (AMR) AF: 0.00 AC: 0 AN: 19290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17610

East Asian (EAS) AF: 0.00 AC: 0 AN: 33886

South Asian (SAS) AF: 0.00 AC: 0 AN: 56478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3282

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 843046

Other (OTH) AF: 0.00 AC: 0 AN: 46640

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.21
PhyloP100		-0.77

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

Other links and lift over

dbSNP: rs4604006; hg19: chr4-177608775;