9-120941616-C-T

Position:

• chr9-120941616-C-T

Variant summary

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

The ENST00000696281.1(C5):​c.*548-7662G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0773 in 152,256 control chromosomes in the GnomAD database, including 1,049 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 0.077 (1049 hom., cov: 32)
• Consequence: C5 ENST00000696281.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C5	ENST00000696281.1	c.*548-7662G>A		intron_variant
C5	ENST00000696279.1	c.*5766-7662G>A		intron_variant, NMD_transcript_variant
C5	ENST00000697922.1	c.*5569-7662G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11745 AN: 152138 Hom.: 1042 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0651

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

GnomAD4 genome AF: 0.0774 AC: 11777 AN: 152256 Hom.: 1049 Cov.: 32 AF XY: 0.0766 AC XY: 5702 AN XY: 74450

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.0337

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.0433

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.0157

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0248 Hom.: 358

Bravo AF: 0.0839

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10985097; hg19: chr9-123703894;