chr4-176685497-T-C

Variant names:

• chr4-176685497-T-C
• rs17697305
• NM_005429.5:c.1146-1457A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.91).
• 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3551 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	NM_005429.5	MANE Select	c.1146-1457A>G		intron	N/A	NP_005420.1	P49767
	HAFML	NR_183975.1		n.182+15788T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.1146-1457A>G		intron	N/A	ENSP00000480043.1	P49767
	HAFML	ENST00000504017.6	TSL:2	n.243+5747T>C		intron	N/A
	HAFML	ENST00000509194.2	TSL:3	n.155+15788T>C		intron	N/A

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

African (AFR) AF: 0.00621 AC: 258 AN: 41572

American (AMR) AF: 0.0228 AC: 348 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3464

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0114 AC: 55 AN: 4818

European-Finnish (FIN) AF: 0.0305 AC: 324 AN: 10610

Middle Eastern (MID) AF: 0.0107 AC: 3 AN: 280

European-Non Finnish (NFE) AF: 0.0358 AC: 2432 AN: 67994

Other (OTH) AF: 0.0246 AC: 52 AN: 2110

Alfa AF: 0.0321 Hom.: 113

Bravo AF: 0.0218

Asia WGS AF: 0.00407 AC: 14 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.71
PhyloP100		-0.025
Mutation Taster		=99/1	polymorphism

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: rs17697305; hg19: chr4-177606651;