9-120933004-C-T

Position:

• chr9-120933004-C-T

Variant summary

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

The ENST00000696281(C5):​c.*1498G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,954 control chromosomes in the GnomAD database, including 32,921 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 0.66 (32921 hom., cov: 32)
• Consequence: C5 ENST00000696281 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495

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 (SAS) allele frequency at 95% confidence interval = 0.794 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	c.*1498G>A		3_prime_UTR_variant	42/42			ENSP00000512521.1
C5	ENST00000696279.1	n.*6716G>A		non_coding_transcript_exon_variant	43/43			ENSP00000512520.1
C5	ENST00000696280.1	n.6618G>A		non_coding_transcript_exon_variant	42/42

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99716 AN: 151834 Hom.: 32881 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.688

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

GnomAD4 genome AF: 0.657 AC: 99806 AN: 151954 Hom.: 32921 Cov.: 32 AF XY: 0.658 AC XY: 48892 AN XY: 74254

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.686

Alfa AF: 0.598 Hom.: 2797

Bravo AF: 0.662

Asia WGS AF: 0.765 AC: 2647 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.6
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10739580; hg19: chr9-123695282;