rs2300929

Variant names:

• chr9-120954562-T-C
• rs2300929
• NM_001735.3:c.4763-694A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-120954562-T-C
• chr9-120954562-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001735.3(C5):​c.4763-694A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,154 control chromosomes in the GnomAD database, including 5,295 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 0.20 (5295 hom., cov: 32)
• Consequence: C5 NM_001735.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5	NM_001735.3	c.4763-694A>G		intron_variant	Intron 39 of 40	ENST00000223642.3	NP_001726.2
C5	NM_001317163.2	c.4781-694A>G		intron_variant	Intron 39 of 40		NP_001304092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000223642.3	c.4763-694A>G		intron_variant	Intron 39 of 40	1	NM_001735.3	ENSP00000223642.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30185 AN: 152034 Hom.: 5265 Cov.: 32

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0346

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.199 AC: 30259 AN: 152154 Hom.: 5295 Cov.: 32 AF XY: 0.194 AC XY: 14460 AN XY: 74404

African (AFR) AF: 0.471 AC: 19528 AN: 41454

American (AMR) AF: 0.127 AC: 1941 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 283 AN: 3470

East Asian (EAS) AF: 0.218 AC: 1128 AN: 5186

South Asian (SAS) AF: 0.124 AC: 597 AN: 4822

European-Finnish (FIN) AF: 0.0346 AC: 367 AN: 10616

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0879 AC: 5980 AN: 67994

Other (OTH) AF: 0.160 AC: 339 AN: 2116

Alfa AF: 0.118 Hom.: 2258

Bravo AF: 0.216

Asia WGS AF: 0.204 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.1
DANN	Benign	0.44
PhyloP100		-0.023
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2300929; hg19: chr9-123716840;