rs16910280

Variant names:

• chr9-121042498-C-T
• rs16910280
• NM_001735.3:c.421+506G>A

Variant summary

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

The NM_001735.3(C5):​c.421+506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,170 control chromosomes in the GnomAD database, including 1,265 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 0.12 (1265 hom., cov: 32)
• Consequence: C5 NM_001735.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001735.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5	NM_001735.3	MANE Select	c.421+506G>A		intron	N/A	NP_001726.2
	C5	NM_001317163.2		c.439+506G>A		intron	N/A	NP_001304092.1
	C5	NM_001317164.2		c.421+506G>A		intron	N/A	NP_001304093.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5	ENST00000223642.3	TSL:1 MANE Select	c.421+506G>A		intron	N/A	ENSP00000223642.1
	C5	ENST00000696284.1		n.1808G>A		non_coding_transcript_exon	Exon 5 of 5
	C5	ENST00000696281.1		c.439+506G>A		intron	N/A	ENSP00000512521.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17549 AN: 152052 Hom.: 1266 Cov.: 32

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.0723

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.115 AC: 17550 AN: 152170 Hom.: 1265 Cov.: 32 AF XY: 0.114 AC XY: 8509 AN XY: 74394

African (AFR) AF: 0.0379 AC: 1574 AN: 41536

American (AMR) AF: 0.171 AC: 2616 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 446 AN: 3472

East Asian (EAS) AF: 0.180 AC: 935 AN: 5182

South Asian (SAS) AF: 0.170 AC: 819 AN: 4820

European-Finnish (FIN) AF: 0.0723 AC: 766 AN: 10592

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9952 AN: 67974

Other (OTH) AF: 0.144 AC: 304 AN: 2110

Alfa AF: 0.121 Hom.: 196

Bravo AF: 0.121

Asia WGS AF: 0.168 AC: 581 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.4
DANN	Benign	0.36
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs16910280; hg19: chr9-123804776;