9-120941890-C-T

Position:

• chr9-120941890-C-T

Variant summary

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

The ENST00000696281.1(C5):​c.*548-7936G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 152,238 control chromosomes in the GnomAD database, including 80 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 0.012 (80 hom., cov: 32)
• Consequence: C5 ENST00000696281.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000696281.1	c.*548-7936G>A		intron_variant				ENSP00000512521
C5	ENST00000696279.1	c.*5766-7936G>A		intron_variant, NMD_transcript_variant				ENSP00000512520
C5	ENST00000697922.1	c.*5569-7936G>A		intron_variant, NMD_transcript_variant				ENSP00000513478

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1847 AN: 152120 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.00280

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0816

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00491

Gnomad OTH AF: 0.0153

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

GnomAD4 genome AF: 0.0121 AC: 1849 AN: 152238 Hom.: 80 Cov.: 32 AF XY: 0.0132 AC XY: 986 AN XY: 74438

Gnomad4 AFR AF: 0.00279

Gnomad4 AMR AF: 0.0817

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00491

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00172 Hom.: 0

Bravo AF: 0.0192

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.87
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4837803; hg19: chr9-123704168;