rs2416808

Positions:

• chr9-120944005-G-A

Variant summary

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

The NR_148450.1(C5-OT1):​n.641-496C>T 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 0.455 in 151,916 control chromosomes in the GnomAD database, including 18,141 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 0.45 (18141 hom., cov: 31)
• Consequence: C5-OT1 NR_148450.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C5-OT1	NR_148450.1	n.641-496C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000696281.1	c.*547+8187C>T		intron_variant				ENSP00000512521
C5	ENST00000696279.1	c.*5765+8187C>T		intron_variant, NMD_transcript_variant				ENSP00000512520
C5	ENST00000697922.1	c.*5568+8187C>T		intron_variant, NMD_transcript_variant				ENSP00000513478

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69017 AN: 151796 Hom.: 18127 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.455 AC: 69051 AN: 151916 Hom.: 18141 Cov.: 31 AF XY: 0.461 AC XY: 34243 AN XY: 74232

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.499

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.541

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.524

Alfa AF: 0.521 Hom.: 6682

Bravo AF: 0.443

Asia WGS AF: 0.561 AC: 1949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.99
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2416808; hg19: chr9-123706283; COSMIC: COSV60401110;