5-77048174-T-C

Position:

• chr5-77048174-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018046.5(AGGF1):​c.1215T>C​(p.Ile405=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,606,922 control chromosomes in the GnomAD database, including 51,954 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 0.24 (4428 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47526 hom.)
• Consequence: AGGF1 NM_018046.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

Genes affected

AGGF1 (HGNC:24684): (angiogenic factor with G-patch and FHA domains 1) This gene encodes an angiogenic factor that promotes proliferation of endothelial cells. Mutations in this gene are associated with a susceptibility to Klippel-Trenaunay syndrome. Pseudogenes of this gene are found on chromosomes 3, 4, 10 and 16.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=-0.047 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGGF1	NM_018046.5	c.1215T>C	p.Ile405=	synonymous_variant	7/14	ENST00000312916.12	NP_060516.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGGF1	ENST00000312916.12	c.1215T>C	p.Ile405=	synonymous_variant	7/14	1	NM_018046.5	ENSP00000316109	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36469 AN: 151918 Hom.: 4430 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.229

GnomAD3 exomes AF: 0.242 AC: 60912 AN: 251380 Hom.: 7590 AF XY: 0.242 AC XY: 32874 AN XY: 135878

Gnomad AFR exome AF: 0.228

Gnomad AMR exome AF: 0.282

Gnomad ASJ exome AF: 0.231

Gnomad EAS exome AF: 0.158

Gnomad SAS exome AF: 0.246

Gnomad FIN exome AF: 0.195

Gnomad NFE exome AF: 0.255

Gnomad OTH exome AF: 0.242

GnomAD4 exome AF: 0.252 AC: 366727 AN: 1454886 Hom.: 47526 Cov.: 31 AF XY: 0.252 AC XY: 182219 AN XY: 724122

Gnomad4 AFR exome AF: 0.214

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.245

GnomAD4 genome AF: 0.240 AC: 36484 AN: 152036 Hom.: 4428 Cov.: 32 AF XY: 0.236 AC XY: 17568 AN XY: 74314

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.227

Alfa AF: 0.250 Hom.: 6409

Bravo AF: 0.242

Asia WGS AF: 0.202 AC: 702 AN: 3478

EpiCase AF: 0.255

EpiControl AF: 0.249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.6
DANN	Benign	0.75

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: rs13155212; hg19: chr5-76343999; COSMIC: COSV57228315;