19-6722624-C-T

Variant names:

• chr19-6722624-C-T
• rs163913
• ENST00000600744.1:c.-50+817G>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+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
• Publications: 21 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=-0.92).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C3	ENST00000600744.1	c.-50+817G>A		intron_variant	Intron 2 of 3	5		ENSP00000472044.1

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

African (AFR) AF: 0.831 AC: 34474 AN: 41486

American (AMR) AF: 0.745 AC: 11381 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.846 AC: 2934 AN: 3470

East Asian (EAS) AF: 0.661 AC: 3418 AN: 5174

South Asian (SAS) AF: 0.664 AC: 3203 AN: 4824

European-Finnish (FIN) AF: 0.844 AC: 8940 AN: 10594

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53950 AN: 68024

Other (OTH) AF: 0.776 AC: 1643 AN: 2116

Alfa AF: 0.787 Hom.: 58155

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
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs163913; hg19: chr19-6722635;