rs2300932

Variant names:

• chr9-121008158-A-C
• rs2300932
• NM_001735.3:c.2348+250T>G

Your query was ambiguous. Multiple possible variants found:

• chr9-121008158-A-C
• chr9-121008158-A-G
• chr9-121008158-A-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.2348+250T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,014 control chromosomes in the GnomAD database, including 29,685 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 0.62 (29685 hom., cov: 32)
• Consequence: C5 NM_001735.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 12 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 (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5	NM_001735.3	c.2348+250T>G		intron_variant	Intron 18 of 40	ENST00000223642.3	NP_001726.2
C5	NM_001317163.2	c.2366+250T>G		intron_variant	Intron 18 of 40		NP_001304092.1
C5	NM_001317164.2	c.2348+250T>G		intron_variant	Intron 18 of 20		NP_001304093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000223642.3	c.2348+250T>G		intron_variant	Intron 18 of 40	1	NM_001735.3	ENSP00000223642.1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94621 AN: 151896 Hom.: 29645 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.623 AC: 94718 AN: 152014 Hom.: 29685 Cov.: 32 AF XY: 0.627 AC XY: 46577 AN XY: 74296

African (AFR) AF: 0.614 AC: 25467 AN: 41448

American (AMR) AF: 0.622 AC: 9499 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 2191 AN: 3468

East Asian (EAS) AF: 0.813 AC: 4212 AN: 5178

South Asian (SAS) AF: 0.753 AC: 3636 AN: 4826

European-Finnish (FIN) AF: 0.638 AC: 6736 AN: 10552

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.602 AC: 40906 AN: 67962

Other (OTH) AF: 0.606 AC: 1276 AN: 2106

Alfa AF: 0.615 Hom.: 119222

Bravo AF: 0.620

Asia WGS AF: 0.763 AC: 2650 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.10
DANN	Benign	0.31
PhyloP100		-2.5
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: rs2300932; hg19: chr9-123770436;