9-120944104-T-C

Variant summary

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

The NR_148450.1(C5-OT1):n.641-595A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,970 control chromosomes in the GnomAD database, including 32,869 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 0.66 (32869 hom., cov: 31)
• Consequence: C5-OT1 NR_148450.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C5-OT1	NR_148450.1	n.641-595A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C5	ENST00000696281.1	c.*547+8088A>G		intron_variant
C5	ENST00000696279.1	c.*5765+8088A>G		intron_variant, NMD_transcript_variant
C5	ENST00000697922.1	c.*5568+8088A>G		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99591 AN: 151852 Hom.: 32829 Cov.: 31

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.806

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.656 AC: 99681 AN: 151970 Hom.: 32869 Cov.: 31 AF XY: 0.657 AC XY: 48833 AN XY: 74274

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.576

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.687

Alfa AF: 0.662 Hom.: 20986

Bravo AF: 0.662

Asia WGS AF: 0.766 AC: 2663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.30
Dann	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2900180; hg19: chr9-123706382;