4-176688110-C-T

Variant names:

• chr4-176688110-C-T
• rs2333495
• NM_005429.5:c.705-183G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005429.5(VEGFC):​c.705-183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 151,792 control chromosomes in the GnomAD database, including 28,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.58 (28184 hom., cov: 33)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.59
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-176688110-C-T is Benign according to our data. Variant chr4-176688110-C-T is described in ClinVar as Benign. ClinVar VariationId is 1291748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.716 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	NM_005429.5	MANE Select	c.705-183G>A		intron	N/A	NP_005420.1	P49767
	HAFML	NR_183975.1		n.183-17793C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.705-183G>A		intron	N/A	ENSP00000480043.1	P49767
	HAFML	ENST00000504017.6	TSL:2	n.243+8360C>T		intron	N/A
	HAFML	ENST00000509194.2	TSL:3	n.156-17793C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88752 AN: 151674 Hom.: 28194 Cov.: 33

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.585 AC: 88764 AN: 151792 Hom.: 28184 Cov.: 33 AF XY: 0.594 AC XY: 44044 AN XY: 74176

African (AFR) AF: 0.320 AC: 13255 AN: 41424

American (AMR) AF: 0.582 AC: 8869 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2323 AN: 3454

East Asian (EAS) AF: 0.700 AC: 3610 AN: 5156

South Asian (SAS) AF: 0.737 AC: 3549 AN: 4818

European-Finnish (FIN) AF: 0.750 AC: 7885 AN: 10518

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47186 AN: 67864

Other (OTH) AF: 0.598 AC: 1261 AN: 2110

Alfa AF: 0.496 Hom.: 1528

Bravo AF: 0.559

Asia WGS AF: 0.698 AC: 2424 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.26
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: rs2333495; hg19: chr4-177609264;