rs344550

Positions:

• chr19-6682942-C-G

Variant summary

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

The NM_000064.4(C3):​c.4173-713G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 154,050 control chromosomes in the GnomAD database, including 32,037 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 0.64 (31693 hom., cov: 32)
  • Exomes 𝑓: 0.58 (344 hom.)
• Consequence: C3 NM_000064.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3	NM_000064.4	c.4173-713G>C		intron_variant		ENST00000245907.11	NP_000055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C3	ENST00000245907.11	c.4173-713G>C		intron_variant		1	NM_000064.4	ENSP00000245907	P1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97948 AN: 151980 Hom.: 31672 Cov.: 32

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.659

GnomAD4 exome AF: 0.581 AC: 1135 AN: 1952 Hom.: 344 Cov.: 0 AF XY: 0.574 AC XY: 561 AN XY: 978

Gnomad4 AMR exome AF: 0.555

Gnomad4 EAS exome AF: 0.567

Gnomad4 SAS exome AF: 0.546

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.598

Gnomad4 OTH exome AF: 0.529

GnomAD4 genome AF: 0.644 AC: 98019 AN: 152098 Hom.: 31693 Cov.: 32 AF XY: 0.643 AC XY: 47820 AN XY: 74346

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.579

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.661

Alfa AF: 0.624 Hom.: 3683

Bravo AF: 0.645

Asia WGS AF: 0.672 AC: 2338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.31

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: rs344550; hg19: chr19-6682953;