rs10818488

chr9-120942809-A-G

Variant summary

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

The NR_148450.1(C5-OT1):n.1341T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 152,084 control chromosomes in the GnomAD database, including 21,120 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 0.52 (21120 hom., cov: 32)
• Consequence: C5-OT1 NR_148450.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578

Genes affected

C5-OT1 (HGNC:):

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C5-OT1	NR_148450.1	n.1341T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C5	ENST00000696281.1	c.*548-8855T>C		intron_variant
C5	ENST00000696279.1	c.*5766-8855T>C		intron_variant, NMD_transcript_variant
C5	ENST00000697922.1	c.*5569-8855T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78832 AN: 151966 Hom.: 21103 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.663

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.519 AC: 78881 AN: 152084 Hom.: 21120 Cov.: 32 AF XY: 0.524 AC XY: 38971 AN XY: 74340

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.663

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.568

Alfa AF: 0.572 Hom.: 23950

Bravo AF: 0.515

Asia WGS AF: 0.581 AC: 2019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.9
Dann	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10818488; hg19: chr9-123705087; COSMIC: COSV60401075;