rs1017119

chr9-121045260-T-C

Variant summary

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

The NM_001735.3(C5):c.258+931A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 152,274 control chromosomes in the GnomAD database, including 212 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 0.022 (212 hom., cov: 32)
• Consequence: C5 NM_001735.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.963

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C5	NM_001735.3	c.258+931A>G		intron_variant		ENST00000223642.3
C5	NM_001317163.2	c.276+931A>G		intron_variant
C5	NM_001317164.2	c.258+931A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C5	ENST00000223642.3	c.258+931A>G		intron_variant		1	NM_001735.3	P1

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3350 AN: 152156 Hom.: 209 Cov.: 32

Gnomad AFR AF: 0.00514

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.00246

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00688

Gnomad OTH AF: 0.0268

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

GnomAD4 genome AF: 0.0221 AC: 3362 AN: 152274 Hom.: 212 Cov.: 32 AF XY: 0.0232 AC XY: 1730 AN XY: 74472

Gnomad4 AFR AF: 0.00512

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.00246

Gnomad4 NFE AF: 0.00688

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0348 Hom.: 75

Bravo AF: 0.0342

Asia WGS AF: 0.0710 AC: 246 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.5
Dann	Benign	0.88

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: rs1017119; hg19: chr9-123807538;