rs34400049

Variant names:

• chr5-77063199-C-A
• rs34400049
• NM_018046.5:c.2092C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-77063199-C-A
• chr5-77063199-C-T

Variant summary

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

The NM_018046.5(AGGF1):​c.2092C>A​(p.Pro698Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,613,404 control chromosomes in the GnomAD database, including 61,144 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4484 hom., cov: 31)
  • Exomes 𝑓: 0.27 (56660 hom.)
• Consequence: AGGF1 NM_018046.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 24 publications found

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]

ENSG00000285000 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029018223).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGGF1	NM_018046.5	c.2092C>A	p.Pro698Thr	missense_variant	Exon 14 of 14	ENST00000312916.12	NP_060516.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGGF1	ENST00000312916.12	c.2092C>A	p.Pro698Thr	missense_variant	Exon 14 of 14	1	NM_018046.5	ENSP00000316109.7
ENSG00000285000	ENST00000646704.1	n.1809+1397C>A		intron_variant	Intron 13 of 15			ENSP00000495089.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34486 AN: 151756 Hom.: 4487 Cov.: 31

Gnomad AFR AF: 0.0979

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.266

GnomAD2 exomes AF: 0.254 AC: 63729 AN: 251232 AF XY: 0.251

Gnomad AFR exome AF: 0.0928

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.267

Gnomad FIN exome AF: 0.265

Gnomad NFE exome AF: 0.292

Gnomad OTH exome AF: 0.268

GnomAD4 exome AF: 0.274 AC: 400174 AN: 1461528 Hom.: 56660 Cov.: 40 AF XY: 0.270 AC XY: 196247 AN XY: 727086

African (AFR) AF: 0.0954 AC: 3195 AN: 33476

American (AMR) AF: 0.284 AC: 12692 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 7265 AN: 26132

East Asian (EAS) AF: 0.272 AC: 10799 AN: 39694

South Asian (SAS) AF: 0.136 AC: 11747 AN: 86256

European-Finnish (FIN) AF: 0.270 AC: 14399 AN: 53398

Middle Eastern (MID) AF: 0.265 AC: 1530 AN: 5768

European-Non Finnish (NFE) AF: 0.290 AC: 322427 AN: 1111702

Other (OTH) AF: 0.267 AC: 16120 AN: 60382

GnomAD4 genome AF: 0.227 AC: 34489 AN: 151876 Hom.: 4484 Cov.: 31 AF XY: 0.226 AC XY: 16767 AN XY: 74226

African (AFR) AF: 0.0978 AC: 4052 AN: 41448

American (AMR) AF: 0.275 AC: 4200 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 976 AN: 3470

East Asian (EAS) AF: 0.273 AC: 1403 AN: 5144

South Asian (SAS) AF: 0.138 AC: 665 AN: 4808

European-Finnish (FIN) AF: 0.264 AC: 2783 AN: 10526

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19506 AN: 67918

Other (OTH) AF: 0.269 AC: 568 AN: 2110

Alfa AF: 0.268 Hom.: 12870

Bravo AF: 0.227

TwinsUK AF: 0.287 AC: 1066

ALSPAC AF: 0.296 AC: 1140

ESP6500AA AF: 0.0999 AC: 440

ESP6500EA AF: 0.291 AC: 2499

ExAC AF: 0.248 AC: 30163

Asia WGS AF: 0.215 AC: 749 AN: 3478

EpiCase AF: 0.291

EpiControl AF: 0.295

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.6
DANN	Benign	0.18
DEOGEN2	Benign	0.0056	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.020
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.045
Sift	Benign	0.89	T
Sift4G	Benign	0.96	T
Polyphen		0.22	B
Vest4		0.0090
MPC		0.21
ClinPred		0.0016	T
GERP RS		1.6
Varity_R		0.034
gMVP		0.20
Mutation Taster		=98/2	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: rs34400049; hg19: chr5-76359024; COSMIC: COSV57227721;