9-120939712-G-A

Variant names:

• chr9-120939712-G-A
• rs10760130
• ENST00000696281.1:c.*548-5758C>T

Variant summary

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

The ENST00000696281.1(C5):​c.*548-5758C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,030 control chromosomes in the GnomAD database, including 18,140 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 (18140 hom., cov: 32)
• Consequence: C5 ENST00000696281.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.919
• Publications: 32 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 Gene-Disease associations (from GenCC):

• complement component 5 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 = 0.663 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5	ENST00000696281.1		c.*548-5758C>T		intron	N/A	ENSP00000512521.1
	C5	ENST00000696279.1		n.*5766-5758C>T		intron	N/A	ENSP00000512520.1
	C5	ENST00000696280.1		n.5668-5758C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69060 AN: 151912 Hom.: 18127 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.454 AC: 69092 AN: 152030 Hom.: 18140 Cov.: 32 AF XY: 0.461 AC XY: 34277 AN XY: 74326

African (AFR) AF: 0.169 AC: 7006 AN: 41452

American (AMR) AF: 0.565 AC: 8618 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2299 AN: 3472

East Asian (EAS) AF: 0.497 AC: 2574 AN: 5182

South Asian (SAS) AF: 0.682 AC: 3285 AN: 4816

European-Finnish (FIN) AF: 0.542 AC: 5726 AN: 10568

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37897 AN: 67964

Other (OTH) AF: 0.525 AC: 1107 AN: 2110

Alfa AF: 0.530 Hom.: 18472

Bravo AF: 0.443

Asia WGS AF: 0.559 AC: 1943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.36
DANN	Benign	0.47
PhyloP100		-0.92

Splicing

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

Other links and lift over

dbSNP: rs10760130; hg19: chr9-123701990; COSMIC: COSV60401065;