9-121019860-C-T

Position:

• chr9-121019860-C-T

Variant summary

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

The ENST00000223642.3(C5):​c.1506+116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 692,742 control chromosomes in the GnomAD database, including 143,966 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 0.63 (30538 hom., cov: 32)
  • Exomes 𝑓: 0.65 (113428 hom.)
• Consequence: C5 ENST00000223642.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C5	NM_001735.3	c.1506+116G>A		intron_variant		ENST00000223642.3	NP_001726.2
C5	NM_001317163.2	c.1524+116G>A		intron_variant			NP_001304092.1
C5	NM_001317164.2	c.1506+116G>A		intron_variant			NP_001304093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000223642.3	c.1506+116G>A		intron_variant		1	NM_001735.3	ENSP00000223642	P1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96135 AN: 151900 Hom.: 30502 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.620

GnomAD4 exome AF: 0.645 AC: 348787 AN: 540724 Hom.: 113428 AF XY: 0.652 AC XY: 187657 AN XY: 288016

Gnomad4 AFR exome AF: 0.619

Gnomad4 AMR exome AF: 0.654

Gnomad4 ASJ exome AF: 0.631

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.742

Gnomad4 FIN exome AF: 0.629

Gnomad4 NFE exome AF: 0.623

Gnomad4 OTH exome AF: 0.641

GnomAD4 genome AF: 0.633 AC: 96231 AN: 152018 Hom.: 30538 Cov.: 32 AF XY: 0.636 AC XY: 47245 AN XY: 74322

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.643

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.620

Alfa AF: 0.629 Hom.: 7712

Bravo AF: 0.631

Asia WGS AF: 0.734 AC: 2551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.2
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2241004; hg19: chr9-123782138;