19-6702011-G-C

Position:

• chr19-6702011-G-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.2440+116C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 724,746 control chromosomes in the GnomAD database, including 157,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33387 hom., cov: 31)
  • Exomes 𝑓: 0.65 (124231 hom.)
• Consequence: C3 NM_000064.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0150

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-6702011-G-C is Benign according to our data. Variant chr19-6702011-G-C is described in ClinVar as [Benign]. Clinvar id is 1192553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3	NM_000064.4	c.2440+116C>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.2440+116C>G		intron_variant		1	NM_000064.4	ENSP00000245907	P1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100105 AN: 151848 Hom.: 33349 Cov.: 31

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.677

GnomAD4 exome AF: 0.652 AC: 373672 AN: 572780 Hom.: 124231 AF XY: 0.651 AC XY: 203102 AN XY: 311826

Gnomad4 AFR exome AF: 0.709

Gnomad4 AMR exome AF: 0.790

Gnomad4 ASJ exome AF: 0.590

Gnomad4 EAS exome AF: 0.868

Gnomad4 SAS exome AF: 0.702

Gnomad4 FIN exome AF: 0.559

Gnomad4 NFE exome AF: 0.617

Gnomad4 OTH exome AF: 0.649

GnomAD4 genome AF: 0.659 AC: 100200 AN: 151966 Hom.: 33387 Cov.: 31 AF XY: 0.662 AC XY: 49138 AN XY: 74282

Gnomad4 AFR AF: 0.705

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.673

Alfa AF: 0.494 Hom.: 1259

Bravo AF: 0.675

Asia WGS AF: 0.765 AC: 2659 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Age related macular degeneration 9 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

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	-0.80
CADD	Benign	4.3
DANN	Benign	0.71

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: rs408290; hg19: chr19-6702022;