rs17697305

chr4-176685497-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005429.5(VEGFC):c.1146-1457A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0233 in 152,232 control chromosomes in the GnomAD database, including 64 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 0.023 (64 hom., cov: 33)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0233 (3551/152232) while in subpopulation NFE AF= 0.0358 (2432/67994). AF 95% confidence interval is 0.0346. There are 64 homozygotes in gnomad4. There are 1692 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 3553 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VEGFC	NM_005429.5	c.1146-1457A>G		intron_variant		ENST00000618562.2
HAFML	NR_183975.1	n.182+15788T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VEGFC	ENST00000618562.2	c.1146-1457A>G		intron_variant		1	NM_005429.5	P1
HAFML	ENST00000509194.1	n.89+15788T>C		intron_variant, non_coding_transcript_variant		3
HAFML	ENST00000504017.5	n.140+5747T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3553 AN: 152112 Hom.: 64 Cov.: 33

Gnomad AFR AF: 0.00622

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0228

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0305

Gnomad MID AF: 0.0134

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0249

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

GnomAD4 genome AF: 0.0233 AC: 3551 AN: 152232 Hom.: 64 Cov.: 33 AF XY: 0.0227 AC XY: 1692 AN XY: 74442

Gnomad4 AFR AF: 0.00621

Gnomad4 AMR AF: 0.0228

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0305

Gnomad4 NFE AF: 0.0358

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0271 Hom.: 9

Bravo AF: 0.0218

Asia WGS AF: 0.00407 AC: 14 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.6
Dann	Benign	0.71

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: rs17697305; hg19: chr4-177606651;