rs2241392

Variant names:

• chr19-6685972-G-C
• rs2241392
• NM_000064.4:c.3810+152C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• atypical hemolytic-uremic syndrome with C3 anomaly

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• complement component 3 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet
• C3 glomerulonephritis

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ENSG00000297005 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000064.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3	NM_000064.4	MANE Select	c.3810+152C>G		intron	N/A	NP_000055.2	P01024

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3	ENST00000245907.11	TSL:1 MANE Select	c.3810+152C>G		intron	N/A	ENSP00000245907.4	P01024
	C3	ENST00000952696.1		c.3822+152C>G		intron	N/A	ENSP00000622755.1
	C3	ENST00000879543.1		c.3807+152C>G		intron	N/A	ENSP00000549602.1

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

African (AFR) AF: 0.404 AC: 7254 AN: 17968

American (AMR) AF: 0.425 AC: 16532 AN: 38874

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 7191 AN: 19452

East Asian (EAS) AF: 0.743 AC: 26285 AN: 35394

South Asian (SAS) AF: 0.449 AC: 29656 AN: 66074

European-Finnish (FIN) AF: 0.437 AC: 19512 AN: 44668

Middle Eastern (MID) AF: 0.382 AC: 977 AN: 2556

European-Non Finnish (NFE) AF: 0.358 AC: 143109 AN: 399544

Other (OTH) AF: 0.390 AC: 13171 AN: 33758

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

African (AFR) AF: 0.407 AC: 16868 AN: 41456

American (AMR) AF: 0.394 AC: 6031 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1304 AN: 3470

East Asian (EAS) AF: 0.707 AC: 3656 AN: 5170

South Asian (SAS) AF: 0.450 AC: 2170 AN: 4824

European-Finnish (FIN) AF: 0.447 AC: 4727 AN: 10566

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24624 AN: 67986

Other (OTH) AF: 0.397 AC: 838 AN: 2112

Alfa AF: 0.360 Hom.: 1394

Bravo AF: 0.400

Asia WGS AF: 0.538 AC: 1868 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.086
DANN	Benign	0.64
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2241392; hg19: chr19-6685983;