5-77034526-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018046.5(AGGF1):c.313+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00401 in 1,574,058 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (90 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (86 hom.)
• Consequence: AGGF1 NM_018046.5 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0002120
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.936

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 5-77034526-T-C is Benign according to our data. Variant chr5-77034526-T-C is described in ClinVar as [Benign]. Clinvar id is 776048.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGGF1	NM_018046.5	c.313+6T>C		splice_donor_region_variant, intron_variant		ENST00000312916.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGGF1	ENST00000312916.12	c.313+6T>C		splice_donor_region_variant, intron_variant		1	NM_018046.5	P1
AGGF1	ENST00000506806.1	c.313+6T>C		splice_donor_region_variant, intron_variant		1
AGGF1	ENST00000502408.1	c.*39+6T>C		splice_donor_region_variant, intron_variant, NMD_transcript_variant		1
AGGF1	ENST00000503538.5	n.330+6T>C		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 3003 AN: 152204 Hom.: 90 Cov.: 33

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00916

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00578 AC: 1452 AN: 251340 Hom.: 39 AF XY: 0.00453 AC XY: 615 AN XY: 135848

Gnomad AFR exome AF: 0.0681

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.0145

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00232 AC: 3305 AN: 1421736 Hom.: 86 Cov.: 25 AF XY: 0.00207 AC XY: 1472 AN XY: 710050

Gnomad4 AFR exome AF: 0.0673

Gnomad4 AMR exome AF: 0.00416

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000222

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000198

Gnomad4 OTH exome AF: 0.00564

GnomAD4 genome AF: 0.0198 AC: 3013 AN: 152322 Hom.: 90 Cov.: 33 AF XY: 0.0187 AC XY: 1391 AN XY: 74478

Gnomad4 AFR AF: 0.0667

Gnomad4 AMR AF: 0.00908

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0114 Hom.: 20

Bravo AF: 0.0225

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.2
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00021
dbscSNV1_RF	Benign	0.098
SpliceAI score (max)		0.010		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: rs77434353; hg19: chr5-76330351; COSMIC: COSV104397832;