rs344540

Positions:

• chr19-6687757-G-A
• chr19-6687757-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.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

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=-0.88).
• 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/exons	MANE	Protein	UniProt
C3	NM_000064.4	c.3490-855C>T		intron_variant		ENST00000245907.11	NP_000055.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C3	ENST00000245907.11	c.3490-855C>T		intron_variant		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

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.912

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.409

Alfa AF: 0.409 Hom.: 2564

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

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: rs344540; hg19: chr19-6687768;