NM_005429.5:c.704+11543A>C

Variant names:

• chr4-176699956-T-G
• rs3775195
• NM_005429.5:c.704+11543A>C

Variant summary

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

The NM_005429.5(VEGFC):​c.704+11543A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,144 control chromosomes in the GnomAD database, including 44,282 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 0.76 (44282 hom., cov: 33)
• Consequence: VEGFC NM_005429.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 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.704+11543A>C		intron	N/A	NP_005420.1
	HAFML	NR_183975.1		n.183-5947T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VEGFC	ENST00000618562.2	TSL:1 MANE Select	c.704+11543A>C		intron	N/A	ENSP00000480043.1
	HAFML	ENST00000504017.6	TSL:2	n.244-5947T>G		intron	N/A
	VEGFC	ENST00000507638.1	TSL:3	n.404-10301A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115516 AN: 152026 Hom.: 44233 Cov.: 33

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.722

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.760 AC: 115622 AN: 152144 Hom.: 44282 Cov.: 33 AF XY: 0.756 AC XY: 56191 AN XY: 74360

African (AFR) AF: 0.845 AC: 35108 AN: 41540

American (AMR) AF: 0.724 AC: 11065 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2732 AN: 3468

East Asian (EAS) AF: 0.954 AC: 4933 AN: 5172

South Asian (SAS) AF: 0.701 AC: 3381 AN: 4824

European-Finnish (FIN) AF: 0.648 AC: 6840 AN: 10560

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.722 AC: 49089 AN: 67990

Other (OTH) AF: 0.765 AC: 1613 AN: 2108

Alfa AF: 0.736 Hom.: 67530

Bravo AF: 0.792

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.37
DANN	Benign	0.51
PhyloP100		-0.42
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: rs3775195; hg19: chr4-177621110;