chr4-176688110-C-T

Position:

• chr4-176688110-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VEGFC	NM_005429.5	c.705-183G>A		intron_variant		ENST00000618562.2	NP_005420.1
HAFML	NR_183975.1	n.183-17793C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VEGFC	ENST00000618562.2	c.705-183G>A		intron_variant		1	NM_005429.5	ENSP00000480043	P1
HAFML	ENST00000509194.1	n.90-17793C>T		intron_variant, non_coding_transcript_variant		3
HAFML	ENST00000504017.5	n.140+8360C>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.700

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.598

Alfa AF: 0.496 Hom.: 1528

Bravo AF: 0.559

Asia WGS AF: 0.698 AC: 2424 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.26

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: rs2333495; hg19: chr4-177609264;