rs11569393

chr19-6721629-A-Cchr19-6721629-A-T

Variant summary

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

The ENST00000600744.1(C3):c.-50+1812T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,904 control chromosomes in the GnomAD database, including 12,168 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 0.36 (12168 hom., cov: 32)
• Consequence: C3 ENST00000600744.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.729

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 (NFE) allele frequency at 95% confidence interval = 0.497 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.-50+1812T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55280 AN: 151786 Hom.: 12166 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.364 AC: 55278 AN: 151904 Hom.: 12168 Cov.: 32 AF XY: 0.364 AC XY: 27027 AN XY: 74194

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.189

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.378

Alfa AF: 0.409 Hom.: 1736

Bravo AF: 0.339

Asia WGS AF: 0.273 AC: 951 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	2.7
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11569393; hg19: chr19-6721640;