9-121064057-C-G

Variant names:

• chr9-121064057-C-G
• rs1323472
• NM_001317163.2:c.83+10697G>C

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+10697G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,792 control chromosomes in the GnomAD database, including 22,330 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 0.51 (22330 hom., cov: 32)
• Consequence: C5 NM_001317163.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5	NM_001317163.2	c.83+10697G>C		intron_variant	Intron 1 of 40		NP_001304092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000696281.1	c.83+10697G>C		intron_variant	Intron 1 of 41			ENSP00000512521.1
C5	ENST00000696279.1	n.*334+3086G>C		intron_variant	Intron 2 of 42			ENSP00000512520.1
C5	ENST00000696280.1	n.154+10974G>C		intron_variant	Intron 1 of 41

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77732 AN: 151670 Hom.: 22315 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.512 AC: 77780 AN: 151792 Hom.: 22330 Cov.: 32 AF XY: 0.521 AC XY: 38582 AN XY: 74120

African (AFR) AF: 0.242 AC: 10049 AN: 41486

American (AMR) AF: 0.674 AC: 10282 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2252 AN: 3468

East Asian (EAS) AF: 0.738 AC: 3807 AN: 5156

South Asian (SAS) AF: 0.801 AC: 3865 AN: 4824

European-Finnish (FIN) AF: 0.579 AC: 6067 AN: 10470

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.581 AC: 39394 AN: 67838

Other (OTH) AF: 0.571 AC: 1201 AN: 2104

Alfa AF: 0.377 Hom.: 1032

Bravo AF: 0.510

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.43
PhyloP100		0.011

Splicing

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

Other links and lift over

dbSNP: rs1323472; hg19: chr9-123826335; COSMIC: COSV60401143;