chr4-176689730-T-G

Variant names:

• chr4-176689730-T-G
• rs1485766
• NM_005429.5:c.705-1803A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005429.5(VEGFC):​c.705-1803A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,040 control chromosomes in the GnomAD database, including 12,920 homozygotes. 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: 𝑓 0.38 (12920 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 27 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

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.705-1803A>C		intron	N/A	NP_005420.1
	HAFML	NR_183975.1		n.183-16173T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.705-1803A>C		intron	N/A	ENSP00000480043.1
	HAFML	ENST00000504017.6	TSL:2	n.243+9980T>G		intron	N/A
	VEGFC	ENST00000507638.1	TSL:3	n.404-75A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57706 AN: 151922 Hom.: 12921 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.398

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.380 AC: 57704 AN: 152040 Hom.: 12920 Cov.: 32 AF XY: 0.377 AC XY: 28033 AN XY: 74294

African (AFR) AF: 0.135 AC: 5615 AN: 41522

American (AMR) AF: 0.346 AC: 5280 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 1404 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2612 AN: 5164

South Asian (SAS) AF: 0.486 AC: 2334 AN: 4800

European-Finnish (FIN) AF: 0.436 AC: 4597 AN: 10546

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34457 AN: 67962

Other (OTH) AF: 0.398 AC: 838 AN: 2108

Alfa AF: 0.451 Hom.: 23838

Bravo AF: 0.363

Asia WGS AF: 0.449 AC: 1563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs1485766; hg19: chr4-177610884;