rs2241392

Positions:

• chr19-6685972-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.3810+152C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 810,368 control chromosomes in the GnomAD database, including 68,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (12449 hom., cov: 32)
  • Exomes 𝑓: 0.40 (56257 hom.)
• Consequence: C3 NM_000064.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.25

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=-0.91).
• BP6: Variant 19-6685972-G-C is Benign according to our data. Variant chr19-6685972-G-C is described in ClinVar as [Benign]. Clinvar id is 1266390.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3	NM_000064.4	c.3810+152C>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.3810+152C>G		intron_variant		1	NM_000064.4	ENSP00000245907	P1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60626 AN: 151962 Hom.: 12434 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.393

GnomAD4 exome AF: 0.401 AC: 263687 AN: 658288 Hom.: 56257 AF XY: 0.401 AC XY: 141035 AN XY: 351412

Gnomad4 AFR exome AF: 0.404

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.370

Gnomad4 EAS exome AF: 0.743

Gnomad4 SAS exome AF: 0.449

Gnomad4 FIN exome AF: 0.437

Gnomad4 NFE exome AF: 0.358

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.399 AC: 60687 AN: 152080 Hom.: 12449 Cov.: 32 AF XY: 0.406 AC XY: 30187 AN XY: 74348

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.450

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.397

Alfa AF: 0.360 Hom.: 1394

Bravo AF: 0.400

Asia WGS AF: 0.538 AC: 1868 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.086
DANN	Benign	0.64

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: rs2241392; hg19: chr19-6685983;