rs2416810

Variant names:

• chr9-121022922-G-A
• rs2416810
• NM_001735.3:c.1116+482C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-121022922-G-A
• chr9-121022922-G-C
• chr9-121022922-G-T

Variant summary

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

The NM_001735.3(C5):​c.1116+482C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 151,796 control chromosomes in the GnomAD database, including 4,847 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 0.23 (4847 hom., cov: 30)
• Consequence: C5 NM_001735.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 13 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5	NM_001735.3	c.1116+482C>T		intron_variant	Intron 10 of 40	ENST00000223642.3	NP_001726.2
C5	NM_001317163.2	c.1134+482C>T		intron_variant	Intron 10 of 40		NP_001304092.1
C5	NM_001317164.2	c.1116+482C>T		intron_variant	Intron 10 of 20		NP_001304093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000223642.3	c.1116+482C>T		intron_variant	Intron 10 of 40	1	NM_001735.3	ENSP00000223642.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34896 AN: 151678 Hom.: 4845 Cov.: 30

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0994

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.230 AC: 34938 AN: 151796 Hom.: 4847 Cov.: 30 AF XY: 0.224 AC XY: 16618 AN XY: 74186

African (AFR) AF: 0.388 AC: 16035 AN: 41340

American (AMR) AF: 0.138 AC: 2104 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3466

East Asian (EAS) AF: 0.252 AC: 1302 AN: 5162

South Asian (SAS) AF: 0.127 AC: 611 AN: 4798

European-Finnish (FIN) AF: 0.131 AC: 1382 AN: 10512

Middle Eastern (MID) AF: 0.110 AC: 32 AN: 290

European-Non Finnish (NFE) AF: 0.185 AC: 12576 AN: 67948

Other (OTH) AF: 0.192 AC: 403 AN: 2104

Alfa AF: 0.176 Hom.: 1755

Bravo AF: 0.236

Asia WGS AF: 0.224 AC: 778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.3
DANN	Benign	0.73
PhyloP100		1.0
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: rs2416810; hg19: chr9-123785200; COSMIC: COSV56329247; COSMIC: COSV56329247;