ENST00000696281.1:c.*548-3951A>G

Variant names:

• chr9-120937905-T-C
• rs10760129
• ENST00000696281.1:c.*548-3951A>G

Variant summary

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

The ENST00000696281.1(C5):​c.*548-3951A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,016 control chromosomes in the GnomAD database, including 17,944 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 (17944 hom., cov: 31)
• Consequence: C5 ENST00000696281.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 15 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 Gene-Disease associations (from GenCC):

• complement component 5 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000696281.1	c.*548-3951A>G		intron_variant	Intron 41 of 41			ENSP00000512521.1
C5	ENST00000696279.1	n.*5766-3951A>G		intron_variant	Intron 42 of 42			ENSP00000512520.1
C5	ENST00000696280.1	n.5668-3951A>G		intron_variant	Intron 41 of 41

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67750 AN: 151898 Hom.: 17932 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.446 AC: 67770 AN: 152016 Hom.: 17944 Cov.: 31 AF XY: 0.453 AC XY: 33622 AN XY: 74296

African (AFR) AF: 0.138 AC: 5736 AN: 41476

American (AMR) AF: 0.563 AC: 8594 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2298 AN: 3470

East Asian (EAS) AF: 0.498 AC: 2572 AN: 5168

South Asian (SAS) AF: 0.685 AC: 3300 AN: 4820

European-Finnish (FIN) AF: 0.541 AC: 5704 AN: 10550

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

European-Non Finnish (NFE) AF: 0.558 AC: 37903 AN: 67956

Other (OTH) AF: 0.515 AC: 1081 AN: 2098

Alfa AF: 0.463 Hom.: 4175

Bravo AF: 0.433

Asia WGS AF: 0.558 AC: 1937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.76
PhyloP100		-0.086

Splicing

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

Other links and lift over

dbSNP: rs10760129; hg19: chr9-123700183;