C7

complement C7, the group of Complement system activation components|Sushi domain containing

Basic information

Region (hg38): 5:40909492-41020216

Links

ENSG00000112936 ∙ NCBI:730 ∙ OMIM:217070 ∙ HGNC:1346 ∙ Uniprot:P10643 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complement component 7 deficiency (Strong), mode of inheritance: AR
• complement component 7 deficiency (Strong), mode of inheritance: AR
• complement component 7 deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Complement component 7 deficiency	AR	Allergy/Immunology/Infectious	Antiinfectious prophylaxis (including related to specific immunization strategies) and early and aggressive treatment of infections may be beneficial	Allergy/Immunology/Infectious	3685247; 2792129; 8892662; 8871666; 17407100; 15328683; 21270745; 22123893; 20591074; 22206826

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the C7 gene.

• not provided (20 variants)
• Complement component 7 deficiency (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the C7 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	121	6	129
missense		1	220	6	6	233
nonsense	8	2				10
start loss						0
frameshift	10	3				13
inframe indel			5			5
splice donor/acceptor (+/-2bp)	2	13	1			16
splice region			9	21	2	32
non coding				61	13	74
Total	20	19	228	188	25

Highest pathogenic variant AF is 0.0000854

Variants in C7

This is a list of pathogenic ClinVar variants found in the C7 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-40909621-G-C			Uncertain significance (Nov 23, 2022)
5-40909632-C-T			Likely benign (May 15, 2023)
5-40928563-T-C			Likely benign (Jun 16, 2023)
5-40928578-A-C			Likely pathogenic (Aug 12, 2021)
5-40928582-G-A			Likely benign (Jan 31, 2024)
5-40928594-C-A		Inborn genetic diseases	Uncertain significance (Jul 27, 2022)
5-40928610-A-AT			Pathogenic (Jun 19, 2023)
5-40928612-A-G			Uncertain significance (Aug 21, 2022)
5-40928612-A-T			Likely benign (Sep 26, 2022)
5-40928626-G-GC			Pathogenic (Oct 19, 2021)
5-40931045-C-T			Likely benign (Dec 01, 2023)
5-40931057-G-T			Likely benign (Jun 20, 2022)
5-40931063-G-A		Complement component 7 deficiency	Pathogenic (Oct 04, 2023)
5-40931069-C-T			Uncertain significance (Nov 01, 2023)
5-40931077-G-C		Inborn genetic diseases	Uncertain significance (Dec 21, 2021)
5-40931093-AC-A			Pathogenic (May 03, 2021)
5-40931099-A-G		Inborn genetic diseases	Uncertain significance (Dec 09, 2023)
5-40931103-C-T			Likely benign (Oct 24, 2022)
5-40931110-T-C			Uncertain significance (Jul 31, 2021)
5-40931120-A-G			Uncertain significance (Jul 06, 2022)
5-40931121-T-A			Uncertain significance (Jan 28, 2022)
5-40931122-G-A			Uncertain significance (Aug 26, 2021)
5-40931135-C-T		C7-related disorder	Likely benign (Jan 26, 2024)
5-40931142-A-G			Uncertain significance (Apr 21, 2021)
5-40931151-C-A			Likely benign (Feb 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
C7	protein_coding	protein_coding	ENST00000313164	18	73688

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.07e-14	0.880	124364	0	273	124637	0.00110

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.644	470	432	1.09	0.0000223	5460
Missense in Polyphen		138	136.08	1.0141		1717
Synonymous	-1.98	193	161	1.20	0.00000906	1550
Loss of Function	2.07	29	43.8	0.663	0.00000202	593

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00493	0.00490
Ashkenazi Jewish	0.0000995	0.0000994
East Asian	0.00206	0.00206
Finnish	0.000484	0.000464
European (Non-Finnish)	0.00107	0.00103
Middle Eastern	0.00206	0.00206
South Asian	0.000132	0.000131
Other	0.000876	0.000826

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells. C7 serves as a membrane anchor.
• Disease: DISEASE: Complement component 7 deficiency (C7D) [MIM:610102]: A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. {ECO:0000269|PubMed:8871666, ECO:0000269|PubMed:9218625, ECO:0000269|PubMed:9856499}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Prion diseases - Homo sapiens (human);Complement and coagulation cascades - Homo sapiens (human);Systemic lupus erythematosus - Homo sapiens (human);Allograft Rejection;Human Complement System;Dengue-2 Interactions with Complement and Coagulation Cascades;Complement Activation;Complement and Coagulation Cascades;alternative complement pathway;classical complement pathway;lectin induced complement pathway;Innate Immune System;Immune System;Regulation of Complement cascade;Terminal pathway of complement;Complement cascade (Consensus)

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.598
• rvis_EVS: -0.21
• rvis_percentile_EVS: 37.74

Haploinsufficiency Scores

• pHI: 0.478
• hipred: N
• hipred_score: 0.187
• ghis: 0.506

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.694

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	High	Medium	High

Mouse Genome Informatics

• Gene name: C7

Gene ontology

• Biological process: cellular sodium ion homeostasis;complement activation;complement activation, alternative pathway;complement activation, classical pathway;cytolysis;regulation of complement activation
• Cellular component: extracellular region;membrane attack complex;extracellular exosome