19-6722011-G-T

Position:

• chr19-6722011-G-T

Variant summary

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

The ENST00000600744.1(C3):​c.-50+1430C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,132 control chromosomes in the GnomAD database, including 47,511 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 (47511 hom., cov: 33)
• Consequence: C3 ENST00000600744.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 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+1430C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119963 AN: 152016 Hom.: 47476 Cov.: 33

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.710

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.789 AC: 120047 AN: 152132 Hom.: 47511 Cov.: 33 AF XY: 0.790 AC XY: 58718 AN XY: 74372

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.841

Gnomad4 EAS AF: 0.663

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.771

Alfa AF: 0.785 Hom.: 80288

Bravo AF: 0.783

Asia WGS AF: 0.683 AC: 2376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs339392; hg19: chr19-6722022;