rs2416808

Variant names:

• chr9-120944005-G-A
• rs2416808
• ENST00000696281.1:c.*547+8187C>T

Variant summary

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

The ENST00000696281.1(C5):​c.*547+8187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,916 control chromosomes in the GnomAD database, including 18,141 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 (18141 hom., cov: 31)
• Consequence: C5 ENST00000696281.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 14 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-OT1 (HGNC:53618): (C5 3' UTR overlapping transcript 1)

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 = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5-OT1	NR_148450.1	n.641-496C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000696281.1	c.*547+8187C>T		intron_variant	Intron 41 of 41			ENSP00000512521.1
C5	ENST00000696279.1	n.*5765+8187C>T		intron_variant	Intron 42 of 42			ENSP00000512520.1
C5	ENST00000696280.1	n.5667+8187C>T		intron_variant	Intron 41 of 41

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69017 AN: 151796 Hom.: 18127 Cov.: 31

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.455 AC: 69051 AN: 151916 Hom.: 18141 Cov.: 31 AF XY: 0.461 AC XY: 34243 AN XY: 74232

African (AFR) AF: 0.169 AC: 6989 AN: 41444

American (AMR) AF: 0.565 AC: 8613 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2297 AN: 3470

East Asian (EAS) AF: 0.499 AC: 2571 AN: 5152

South Asian (SAS) AF: 0.690 AC: 3317 AN: 4808

European-Finnish (FIN) AF: 0.541 AC: 5704 AN: 10540

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

European-Non Finnish (NFE) AF: 0.558 AC: 37875 AN: 67936

Other (OTH) AF: 0.524 AC: 1104 AN: 2106

Alfa AF: 0.515 Hom.: 8302

Bravo AF: 0.443

Asia WGS AF: 0.561 AC: 1949 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	0.99
DANN	Benign	0.36
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs2416808; hg19: chr9-123706283; COSMIC: COSV60401110;