chr19-6727354-G-A

Variant names:

• chr19-6727354-G-A
• rs171094
• ENST00000600744.1:c.-373+3183C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000600744.1(C3):​c.-373+3183C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,070 control chromosomes in the GnomAD database, including 27,945 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 0.60 (27945 hom., cov: 32)
• Consequence: C3 ENST00000600744.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889
• Publications: 10 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.651 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.-373+3183C>T		intron	N/A	ENSP00000472044.1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90960 AN: 151952 Hom.: 27943 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.598 AC: 90982 AN: 152070 Hom.: 27945 Cov.: 32 AF XY: 0.601 AC XY: 44645 AN XY: 74316

African (AFR) AF: 0.456 AC: 18908 AN: 41456

American (AMR) AF: 0.638 AC: 9762 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2420 AN: 3472

East Asian (EAS) AF: 0.608 AC: 3136 AN: 5162

South Asian (SAS) AF: 0.501 AC: 2411 AN: 4814

European-Finnish (FIN) AF: 0.727 AC: 7683 AN: 10568

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44608 AN: 67998

Other (OTH) AF: 0.602 AC: 1268 AN: 2108

Alfa AF: 0.627 Hom.: 36752

Bravo AF: 0.586

Asia WGS AF: 0.559 AC: 1940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.76
PhyloP100		-0.89

Splicing

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

Other links and lift over

dbSNP: rs171094; hg19: chr19-6727365;