rs17697359

Variant names:

• chr4-176686185-T-C
• rs17697359
• NM_005429.5:c.1145+1002A>G

Variant summary

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

The NM_005429.5(VEGFC):​c.1145+1002A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0838 in 152,194 control chromosomes in the GnomAD database, including 595 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 0.084 (595 hom., cov: 33)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 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.1145+1002A>G		intron	N/A	NP_005420.1
	HAFML	NR_183975.1		n.182+16476T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.1145+1002A>G		intron	N/A	ENSP00000480043.1
	HAFML	ENST00000504017.6	TSL:2	n.243+6435T>C		intron	N/A
	HAFML	ENST00000509194.2	TSL:3	n.155+16476T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0838 AC: 12738 AN: 152076 Hom.: 594 Cov.: 33

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0793

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0807

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0838 AC: 12747 AN: 152194 Hom.: 595 Cov.: 33 AF XY: 0.0801 AC XY: 5961 AN XY: 74410

African (AFR) AF: 0.0736 AC: 3058 AN: 41530

American (AMR) AF: 0.0614 AC: 938 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0305 AC: 147 AN: 4824

European-Finnish (FIN) AF: 0.0793 AC: 839 AN: 10582

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7053 AN: 68000

Other (OTH) AF: 0.0799 AC: 169 AN: 2116

Alfa AF: 0.0973 Hom.: 649

Bravo AF: 0.0829

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.84
DANN	Benign	0.65
PhyloP100		-1.6
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: rs17697359; hg19: chr4-177607339;