rs163494

Positions:

• chr19-6724329-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000600744.1(C3):​c.-372-566G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,042 control chromosomes in the GnomAD database, including 3,410 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 0.21 (3410 hom., cov: 32)
• Consequence: C3 ENST00000600744.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331

Genes affected

C3 (HGNC:1318): (complement C3) Complement component C3 plays a central role in the activation of complement system. Its activation is required for both classical and alternative complement activation pathways. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form the mature protein, which is then further processed to generate numerous peptide products. The C3a peptide, also known as the C3a anaphylatoxin, modulates inflammation and possesses antimicrobial activity. Mutations in this gene are associated with atypical hemolytic uremic syndrome and age-related macular degeneration in human patients. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C3	ENST00000600744.1	c.-372-566G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31242 AN: 151924 Hom.: 3408 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0387

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.206 AC: 31268 AN: 152042 Hom.: 3410 Cov.: 32 AF XY: 0.201 AC XY: 14958 AN XY: 74332

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.0386

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.187

Alfa AF: 0.206 Hom.: 400

Bravo AF: 0.203

Asia WGS AF: 0.106 AC: 370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.56
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs163494; hg19: chr19-6724340;