rs1548782

Variant names:

• chr9-121007564-T-A
• rs1548782
• NM_001735.3:c.2349-587A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-121007564-T-A
• chr9-121007564-T-C
• chr9-121007564-T-G

Variant summary

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

The NM_001735.3(C5):​c.2349-587A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,058 control chromosomes in the GnomAD database, including 27,691 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 0.60 (27691 hom., cov: 32)
• Consequence: C5 NM_001735.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5	NM_001735.3	c.2349-587A>T		intron_variant	Intron 18 of 40	ENST00000223642.3	NP_001726.2
C5	NM_001317163.2	c.2367-587A>T		intron_variant	Intron 18 of 40		NP_001304092.1
C5	NM_001317164.2	c.2349-587A>T		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.2349-587A>T		intron_variant	Intron 18 of 40	1	NM_001735.3	ENSP00000223642.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91229 AN: 151940 Hom.: 27674 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.776

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.600 AC: 91301 AN: 152058 Hom.: 27691 Cov.: 32 AF XY: 0.604 AC XY: 44870 AN XY: 74332

African (AFR) AF: 0.520 AC: 21564 AN: 41440

American (AMR) AF: 0.630 AC: 9626 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2202 AN: 3466

East Asian (EAS) AF: 0.776 AC: 4011 AN: 5168

South Asian (SAS) AF: 0.750 AC: 3620 AN: 4826

European-Finnish (FIN) AF: 0.639 AC: 6753 AN: 10566

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.610 AC: 41444 AN: 67986

Other (OTH) AF: 0.600 AC: 1267 AN: 2112

Alfa AF: 0.606 Hom.: 3528

Bravo AF: 0.595

Asia WGS AF: 0.724 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.60
DANN	Benign	0.61
PhyloP100		-0.44
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: rs1548782; hg19: chr9-123769842;