rs11569429

chr19-6709063-C-T

Variant summary

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

The NM_000064.4(C3):c.1845+621G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,174 control chromosomes in the GnomAD database, including 1,205 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 0.11 (1205 hom., cov: 31)
• Consequence: C3 NM_000064.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542

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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C3	NM_000064.4	c.1845+621G>A		intron_variant		ENST00000245907.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C3	ENST00000245907.11	c.1845+621G>A		intron_variant		1	NM_000064.4	P1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17377 AN: 152056 Hom.: 1203 Cov.: 31

Gnomad AFR AF: 0.0463

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0834

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.114 AC: 17387 AN: 152174 Hom.: 1205 Cov.: 31 AF XY: 0.115 AC XY: 8558 AN XY: 74382

Gnomad4 AFR AF: 0.0463

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0845

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.135

Alfa AF: 0.138 Hom.: 2637

Bravo AF: 0.108

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	1.8
Dann	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11569429; hg19: chr19-6709074;