19-6685293-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000064.4(C3):c.3811-147C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 739,252 control chromosomes in the GnomAD database, including 61,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (11067 hom., cov: 31)
  • Exomes 𝑓: 0.40 (50148 hom.)
• Consequence: C3 NM_000064.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.503

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-6685293-G-C is Benign according to our data. Variant chr19-6685293-G-C is described in ClinVar as [Benign]. Clinvar id is 1261016.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C3	NM_000064.4	c.3811-147C>G		intron_variant		ENST00000245907.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C3	ENST00000245907.11	c.3811-147C>G		intron_variant		1	NM_000064.4	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56864 AN: 151844 Hom.: 11050 Cov.: 31

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.403 AC: 236758 AN: 587288 Hom.: 50148 AF XY: 0.404 AC XY: 127330 AN XY: 315144

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.669

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.469

Gnomad4 NFE exome AF: 0.374

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.375 AC: 56935 AN: 151964 Hom.: 11067 Cov.: 31 AF XY: 0.382 AC XY: 28360 AN XY: 74252

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.631

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.478

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.372

Alfa AF: 0.379 Hom.: 6336

Bravo AF: 0.368

Asia WGS AF: 0.507 AC: 1760 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.0
Dann	Benign	0.43

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: rs2241393; hg19: chr19-6685304; COSMIC: COSV55574677; COSMIC: COSV55574677;