rs8107911

Positions:

• chr19-6706030-G-A

Variant summary

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

The NM_000064.4(C3):​c.2245+1046C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,240 control chromosomes in the GnomAD database, including 50,668 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 0.81 (50668 hom., cov: 33)
• Consequence: C3 NM_000064.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C3	NM_000064.4	c.2245+1046C>T		intron_variant		ENST00000245907.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C3	ENST00000245907.11	c.2245+1046C>T		intron_variant		1	NM_000064.4	P1

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123737 AN: 152122 Hom.: 50628 Cov.: 33

Gnomad AFR AF: 0.902

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.913

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.813 AC: 123834 AN: 152240 Hom.: 50668 Cov.: 33 AF XY: 0.815 AC XY: 60674 AN XY: 74426

Gnomad4 AFR AF: 0.902

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.827

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.811

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.823

Alfa AF: 0.773 Hom.: 9239

Bravo AF: 0.828

Asia WGS AF: 0.849 AC: 2952 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	0.54
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8107911; hg19: chr19-6706041;