rs344548

Positions:

• chr19-6685806-G-C
• chr19-6685806-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000064.4(C3):​c.3810+318C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,024 control chromosomes in the GnomAD database, including 48,796 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 0.80 (48796 hom., cov: 30)
• Consequence: C3 NM_000064.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3	NM_000064.4	c.3810+318C>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+318C>G		intron_variant		1	NM_000064.4	ENSP00000245907.4

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121167 AN: 151906 Hom.: 48778 Cov.: 30

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.866

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.819

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

GnomAD4 genome AF: 0.797 AC: 121230 AN: 152024 Hom.: 48796 Cov.: 30 AF XY: 0.800 AC XY: 59428 AN XY: 74318

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.867

Gnomad4 ASJ AF: 0.860

Gnomad4 EAS AF: 0.920

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.815

Alfa AF: 0.802 Hom.: 5754

Bravo AF: 0.795

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.72

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: rs344548; hg19: chr19-6685817;