rs344540

Variant names:

• chr19-6687757-G-A
• rs344540
• NM_000064.4:c.3490-855C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-6687757-G-A
• chr19-6687757-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000064.4(C3):​c.3490-855C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,966 control chromosomes in the GnomAD database, including 16,838 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16838 hom., cov: 32)
• Consequence: C3 NM_000064.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 7 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: Labcorp Genetics (formerly Invitae), ClinGen
• complement component 3 deficiency

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

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ENSG00000297005 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C3	NM_000064.4	c.3490-855C>T		intron_variant	Intron 27 of 40	ENST00000245907.11	NP_000055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C3	ENST00000245907.11	c.3490-855C>T		intron_variant	Intron 27 of 40	1	NM_000064.4	ENSP00000245907.4

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68829 AN: 151848 Hom.: 16810 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.407

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.453 AC: 68909 AN: 151966 Hom.: 16838 Cov.: 32 AF XY: 0.461 AC XY: 34223 AN XY: 74256

African (AFR) AF: 0.553 AC: 22928 AN: 41434

American (AMR) AF: 0.394 AC: 6019 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1159 AN: 3470

East Asian (EAS) AF: 0.912 AC: 4729 AN: 5188

South Asian (SAS) AF: 0.592 AC: 2857 AN: 4828

European-Finnish (FIN) AF: 0.431 AC: 4543 AN: 10532

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25242 AN: 67932

Other (OTH) AF: 0.409 AC: 864 AN: 2112

Alfa AF: 0.422 Hom.: 6945

Bravo AF: 0.456

Asia WGS AF: 0.718 AC: 2496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.9
DANN	Benign	0.73
PhyloP100		1.5
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: rs344540; hg19: chr19-6687768;