9-120941616-C-T

Variant names:

• chr9-120941616-C-T
• rs10985097
• ENST00000696281.1:c.*548-7662G>A

Variant summary

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

The ENST00000696281.1(C5):​c.*548-7662G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0773 in 152,256 control chromosomes in the GnomAD database, including 1,049 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 0.077 (1049 hom., cov: 32)
• Consequence: C5 ENST00000696281.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 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.*548-7662G>A		intron_variant	Intron 41 of 41			ENSP00000512521.1
C5	ENST00000696279.1	n.*5766-7662G>A		intron_variant	Intron 42 of 42			ENSP00000512520.1
C5	ENST00000696280.1	n.5668-7662G>A		intron_variant	Intron 41 of 41

Frequencies

GnomAD3 genomes AF: 0.0772 AC: 11745 AN: 152138 Hom.: 1042 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.0441

Gnomad FIN AF: 0.0214

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0651

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

GnomAD4 genome AF: 0.0774 AC: 11777 AN: 152256 Hom.: 1049 Cov.: 32 AF XY: 0.0766 AC XY: 5702 AN XY: 74450

African (AFR) AF: 0.206 AC: 8535 AN: 41508

American (AMR) AF: 0.0337 AC: 516 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1019 AN: 5186

South Asian (SAS) AF: 0.0433 AC: 209 AN: 4826

European-Finnish (FIN) AF: 0.0214 AC: 227 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0157 AC: 1065 AN: 68024

Other (OTH) AF: 0.0639 AC: 135 AN: 2112

Alfa AF: 0.0347 Hom.: 1401

Bravo AF: 0.0839

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.65
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs10985097; hg19: chr9-123703894;