rs1179766

Variant names:

• chr9-121061694-T-C
• rs1179766
• NM_001317163.2:c.83+13060A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

C5 Gene-Disease associations (from GenCC):

• complement component 5 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317163.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5	NM_001317163.2		c.83+13060A>G		intron	N/A	NP_001304092.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5	ENST00000696281.1		c.83+13060A>G		intron	N/A	ENSP00000512521.1
	C5	ENST00000696279.1		n.*335-3697A>G		intron	N/A	ENSP00000512520.1
	C5	ENST00000696280.1		n.154+13337A>G		intron	N/A

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

African (AFR) AF: 0.771 AC: 32007 AN: 41534

American (AMR) AF: 0.954 AC: 14601 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 3391 AN: 3472

East Asian (EAS) AF: 0.996 AC: 5175 AN: 5194

South Asian (SAS) AF: 0.981 AC: 4739 AN: 4830

European-Finnish (FIN) AF: 0.949 AC: 10074 AN: 10610

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.944 AC: 64228 AN: 68036

Other (OTH) AF: 0.923 AC: 1949 AN: 2112

Alfa AF: 0.937 Hom.: 106883

Bravo AF: 0.895

Asia WGS AF: 0.974 AC: 3384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.1
DANN	Benign	0.41
PhyloP100		-0.28

Splicing

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

Other links and lift over

dbSNP: rs1179766; hg19: chr9-123823972;