9-120944104-T-C

Variant names:

• chr9-120944104-T-C
• rs2900180
• ENST00000696281.1:c.*547+8088A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000696281.1(C5):​c.*547+8088A>G variant causes a intron 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 ENST00000696281.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 70 publications found

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]

C5-OT1 (HGNC:53618): (C5 3' UTR overlapping transcript 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000696281.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5-OT1	NR_148450.1		n.641-595A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5	ENST00000696281.1		c.*547+8088A>G		intron	N/A	ENSP00000512521.1	A0A8Q3SID6
	C5	ENST00000696279.1		n.*5765+8088A>G		intron	N/A	ENSP00000512520.1	A0A8Q3SIH6
	C5	ENST00000696280.1		n.5667+8088A>G		intron	N/A

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

African (AFR) AF: 0.650 AC: 26961 AN: 41458

American (AMR) AF: 0.692 AC: 10563 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2579 AN: 3468

East Asian (EAS) AF: 0.720 AC: 3713 AN: 5158

South Asian (SAS) AF: 0.815 AC: 3929 AN: 4818

European-Finnish (FIN) AF: 0.576 AC: 6067 AN: 10538

Middle Eastern (MID) AF: 0.801 AC: 234 AN: 292

European-Non Finnish (NFE) AF: 0.644 AC: 43748 AN: 67956

Other (OTH) AF: 0.687 AC: 1445 AN: 2102

Alfa AF: 0.661 Hom.: 25394

Bravo AF: 0.662

Asia WGS AF: 0.766 AC: 2663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.26
PhyloP100		-2.5

Splicing

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

Other links and lift over

dbSNP: rs2900180; hg19: chr9-123706382;