rs1179766

Positions:

• chr9-121061694-T-C

Variant summary

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

The NM_001317163.2(C5):​c.83+13060A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,298 control chromosomes in the GnomAD database, including 62,425 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 0.90 (62425 hom., cov: 34)
• Consequence: C5 NM_001317163.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284

Genes affected

C5 (HGNC:1331): (complement C5) This gene encodes a component of the complement system, a part of the innate immune system that plays an important role in inflammation, host homeostasis, and host defense against pathogens. The encoded preproprotein is proteolytically processed to generate multiple protein products, including the C5 alpha chain, C5 beta chain, C5a anaphylatoxin and C5b. The C5 protein is comprised of the C5 alpha and beta chains, which are linked by a disulfide bridge. Cleavage of the alpha chain by a convertase enzyme results in the formation of the C5a anaphylatoxin, which possesses potent spasmogenic and chemotactic activity, and the C5b macromolecular cleavage product, a subunit of the membrane attack complex (MAC). Mutations in this gene cause complement component 5 deficiency, a disease characterized by recurrent bacterial infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C5	NM_001317163.2	c.83+13060A>G		intron_variant			NP_001304092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000696281.1	c.83+13060A>G		intron_variant				ENSP00000512521
C5	ENST00000696279.1	c.*335-3697A>G		intron_variant, NMD_transcript_variant				ENSP00000512520
C5	ENST00000697922.1	c.84-3697A>G		intron_variant, NMD_transcript_variant				ENSP00000513478

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137223 AN: 152180 Hom.: 62385 Cov.: 34

Gnomad AFR AF: 0.771

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.944

Gnomad OTH AF: 0.923

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

GnomAD4 genome AF: 0.902 AC: 137321 AN: 152298 Hom.: 62425 Cov.: 34 AF XY: 0.905 AC XY: 67409 AN XY: 74462

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.954

Gnomad4 ASJ AF: 0.977

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.981

Gnomad4 FIN AF: 0.949

Gnomad4 NFE AF: 0.944

Gnomad4 OTH AF: 0.923

Alfa AF: 0.938 Hom.: 91671

Bravo AF: 0.895

Asia WGS AF: 0.974 AC: 3384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.1
DANN	Benign	0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1179766; hg19: chr9-123823972;