rs16910233

chr9-120961333-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001735.3(C5):c.4588+149G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 677,916 control chromosomes in the GnomAD database, including 914 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 0.054 (666 hom., cov: 32)
  • Exomes 𝑓: 0.011 (248 hom.)
• Consequence: C5 NM_001735.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C5	NM_001735.3	c.4588+149G>C		intron_variant		ENST00000223642.3
C5	NM_001317163.2	c.4606+149G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C5	ENST00000223642.3	c.4588+149G>C		intron_variant		1	NM_001735.3	P1

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8267 AN: 152098 Hom.: 665 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00637

Gnomad OTH AF: 0.0378

GnomAD4 exome AF: 0.0106 AC: 5596 AN: 525700 Hom.: 248 AF XY: 0.00900 AC XY: 2548 AN XY: 283062

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.0181

Gnomad4 ASJ exome AF: 0.000390

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000420

Gnomad4 FIN exome AF: 0.000139

Gnomad4 NFE exome AF: 0.00594

Gnomad4 OTH exome AF: 0.0187

GnomAD4 genome AF: 0.0544 AC: 8284 AN: 152216 Hom.: 666 Cov.: 32 AF XY: 0.0535 AC XY: 3979 AN XY: 74432

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.00635

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0342 Hom.: 46

Bravo AF: 0.0615

Asia WGS AF: 0.0140 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	5.0
Dann	Benign	0.60

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: rs16910233; hg19: chr9-123723611;