rs2300929

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• 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/exons	MANE	Protein	UniProt
C5	NM_001735.3	c.4763-694A>G		intron_variant		ENST00000223642.3	NP_001726.2
C5	NM_001317163.2	c.4781-694A>G		intron_variant			NP_001304092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000223642.3	c.4763-694A>G		intron_variant		1	NM_001735.3	ENSP00000223642	P1

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

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0816

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0346

Gnomad4 NFE AF: 0.0879

Gnomad4 OTH AF: 0.160

Alfa AF: 0.101 Hom.: 1135

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2300929; hg19: chr9-123716840;