9-120933004-C-T

Variant names:

• chr9-120933004-C-T
• rs10739580
• ENST00000696279.1:n.*6716G>A

Variant summary

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

The ENST00000696279.1(C5):​n.*6716G>A variant causes a non coding transcript exon 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 ENST00000696279.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495
• Publications: 23 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=-0.86).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000696279.1	n.*6716G>A		non_coding_transcript_exon_variant	Exon 43 of 43			ENSP00000512520.1
C5	ENST00000696280.1	n.6618G>A		non_coding_transcript_exon_variant	Exon 42 of 42
C5	ENST00000697921.1	n.5407G>A		non_coding_transcript_exon_variant	Exon 30 of 30

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

African (AFR) AF: 0.651 AC: 26972 AN: 41402

American (AMR) AF: 0.692 AC: 10581 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2585 AN: 3472

East Asian (EAS) AF: 0.721 AC: 3736 AN: 5182

South Asian (SAS) AF: 0.815 AC: 3932 AN: 4824

European-Finnish (FIN) AF: 0.579 AC: 6084 AN: 10506

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43787 AN: 67966

Other (OTH) AF: 0.686 AC: 1450 AN: 2114

Alfa AF: 0.619 Hom.: 4024

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
PhyloP100		-0.49

Splicing

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

Other links and lift over

dbSNP: rs10739580; hg19: chr9-123695282;