rs12685344

Variant names:

• chr9-121002713-G-A
• rs12685344
• NM_001735.3:c.2562+3206C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-121002713-G-A
• chr9-121002713-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.2562+3206C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 151,978 control chromosomes in the GnomAD database, including 521 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 0.080 (521 hom., cov: 30)
• Consequence: C5 NM_001735.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0929 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.2562+3206C>T		intron	N/A	NP_001726.2
	C5	NM_001317163.2		c.2580+3206C>T		intron	N/A	NP_001304092.1
	C5	NM_001317164.2		c.2563-2662C>T		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.2562+3206C>T		intron	N/A	ENSP00000223642.1
	C5	ENST00000696281.1		c.2580+3206C>T		intron	N/A	ENSP00000512521.1
	C5	ENST00000466280.2	TSL:5	c.1558-2662C>T		intron	N/A	ENSP00000513491.1

Frequencies

GnomAD3 genomes AF: 0.0799 AC: 12136 AN: 151860 Hom.: 522 Cov.: 30

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.0670

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0313

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.0490

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0948

Gnomad OTH AF: 0.0647

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

GnomAD4 genome AF: 0.0799 AC: 12140 AN: 151978 Hom.: 521 Cov.: 30 AF XY: 0.0771 AC XY: 5726 AN XY: 74306

African (AFR) AF: 0.0769 AC: 3186 AN: 41436

American (AMR) AF: 0.0668 AC: 1019 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3466

East Asian (EAS) AF: 0.0310 AC: 160 AN: 5166

South Asian (SAS) AF: 0.0885 AC: 426 AN: 4816

European-Finnish (FIN) AF: 0.0490 AC: 518 AN: 10568

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0948 AC: 6443 AN: 67960

Other (OTH) AF: 0.0649 AC: 137 AN: 2110

Alfa AF: 0.0836 Hom.: 386

Bravo AF: 0.0809

Asia WGS AF: 0.0610 AC: 212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.30
PhyloP100		0.36
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: rs12685344; hg19: chr9-123764991;