ENST00000600744.1:c.-50+1430C>A

Variant names:

• chr19-6722011-G-T
• rs339392
• ENST00000600744.1:c.-50+1430C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 publications found

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]

C3 Gene-Disease associations (from GenCC):

• atypical hemolytic-uremic syndrome with C3 anomaly

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• complement component 3 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine
• C3 glomerulonephritis

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000600744.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3	ENST00000600744.1	TSL:5	c.-50+1430C>A		intron	N/A	ENSP00000472044.1

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

African (AFR) AF: 0.823 AC: 34172 AN: 41512

American (AMR) AF: 0.738 AC: 11287 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2919 AN: 3470

East Asian (EAS) AF: 0.663 AC: 3422 AN: 5164

South Asian (SAS) AF: 0.670 AC: 3233 AN: 4826

European-Finnish (FIN) AF: 0.843 AC: 8908 AN: 10568

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53618 AN: 67994

Other (OTH) AF: 0.771 AC: 1624 AN: 2106

Alfa AF: 0.785 Hom.: 138220

Bravo AF: 0.783

Asia WGS AF: 0.683 AC: 2376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.59
PhyloP100		-0.056

Splicing

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

Other links and lift over

dbSNP: rs339392; hg19: chr19-6722022;