19-6722624-C-T

Variant summary

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

The ENST00000600744.1(C3):c.-50+817G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,174 control chromosomes in the GnomAD database, including 48,135 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 0.79 (48135 hom., cov: 33)
• Consequence: C3 ENST00000600744.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 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+817G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120718 AN: 152056 Hom.: 48095 Cov.: 33

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.794 AC: 120805 AN: 152174 Hom.: 48135 Cov.: 33 AF XY: 0.794 AC XY: 59047 AN XY: 74388

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.846

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.844

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.776

Alfa AF: 0.788 Hom.: 42396

Bravo AF: 0.788

Asia WGS AF: 0.682 AC: 2373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.9
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: rs163913; hg19: chr19-6722635;