19-6679349-T-C

Position:

• chr19-6679349-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000064.4(C3):​c.4546+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 1,484,326 control chromosomes in the GnomAD database, including 449,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (48732 hom., cov: 31)
  • Exomes 𝑓: 0.77 (400362 hom.)
• Consequence: C3 NM_000064.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.581

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-6679349-T-C is Benign according to our data. Variant chr19-6679349-T-C is described in ClinVar as [Benign]. Clinvar id is 1192668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3	NM_000064.4	c.4546+58A>G		intron_variant		ENST00000245907.11	NP_000055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C3	ENST00000245907.11	c.4546+58A>G		intron_variant		1	NM_000064.4	ENSP00000245907.4

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121167 AN: 151956 Hom.: 48680 Cov.: 31

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.724

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.798

GnomAD4 exome AF: 0.774 AC: 1030735 AN: 1332252 Hom.: 400362 Cov.: 20 AF XY: 0.776 AC XY: 519644 AN XY: 669914

Gnomad4 AFR exome AF: 0.899

Gnomad4 AMR exome AF: 0.702

Gnomad4 ASJ exome AF: 0.683

Gnomad4 EAS exome AF: 0.668

Gnomad4 SAS exome AF: 0.831

Gnomad4 FIN exome AF: 0.749

Gnomad4 NFE exome AF: 0.776

Gnomad4 OTH exome AF: 0.771

GnomAD4 genome AF: 0.797 AC: 121276 AN: 152074 Hom.: 48732 Cov.: 31 AF XY: 0.792 AC XY: 58888 AN XY: 74324

Gnomad4 AFR AF: 0.891

Gnomad4 AMR AF: 0.743

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.776

Gnomad4 OTH AF: 0.799

Alfa AF: 0.775 Hom.: 43055

Bravo AF: 0.800

Asia WGS AF: 0.775 AC: 2697 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Age related macular degeneration 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Complement component 3 deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.062
DANN	Benign	0.44

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: rs344555; hg19: chr19-6679360;