chr9-120942809-A-G

Variant names:

• chr9-120942809-A-G
• rs10818488
• ENST00000696281.1:c.*548-8855T>C

Variant summary

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

The ENST00000696281.1(C5):​c.*548-8855T>C variant causes a intron 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 ENST00000696281.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578
• Publications: 87 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.672 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.1341T>C		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5	ENST00000696281.1		c.*548-8855T>C		intron	N/A	ENSP00000512521.1	A0A8Q3SID6
	C5	ENST00000696279.1		n.*5766-8855T>C		intron	N/A	ENSP00000512520.1	A0A8Q3SIH6
	C5	ENST00000696280.1		n.5668-8855T>C		intron	N/A

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

African (AFR) AF: 0.378 AC: 15674 AN: 41490

American (AMR) AF: 0.597 AC: 9129 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2300 AN: 3470

East Asian (EAS) AF: 0.498 AC: 2577 AN: 5170

South Asian (SAS) AF: 0.692 AC: 3338 AN: 4824

European-Finnish (FIN) AF: 0.540 AC: 5709 AN: 10566

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38345 AN: 67966

Other (OTH) AF: 0.568 AC: 1198 AN: 2110

Alfa AF: 0.564 Hom.: 30932

Bravo AF: 0.515

Asia WGS AF: 0.581 AC: 2019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.9
DANN	Benign	0.57
PhyloP100		0.58

Splicing

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

Other links and lift over

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