rs992670

Variant names:

• chr9-121019492-G-A
• rs992670
• NM_001735.3:c.1506+484C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-121019492-G-A
• chr9-121019492-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.1506+484C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,008 control chromosomes in the GnomAD database, including 21,103 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 0.52 (21103 hom., cov: 32)
• Consequence: C5 NM_001735.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5	NM_001735.3	c.1506+484C>T		intron_variant	Intron 12 of 40	ENST00000223642.3	NP_001726.2
C5	NM_001317163.2	c.1524+484C>T		intron_variant	Intron 12 of 40		NP_001304092.1
C5	NM_001317164.2	c.1506+484C>T		intron_variant	Intron 12 of 20		NP_001304093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000223642.3	c.1506+484C>T		intron_variant	Intron 12 of 40	1	NM_001735.3	ENSP00000223642.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79503 AN: 151888 Hom.: 21075 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.524 AC: 79585 AN: 152008 Hom.: 21103 Cov.: 32 AF XY: 0.529 AC XY: 39270 AN XY: 74290

African (AFR) AF: 0.462 AC: 19166 AN: 41442

American (AMR) AF: 0.564 AC: 8613 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1994 AN: 3464

East Asian (EAS) AF: 0.745 AC: 3852 AN: 5168

South Asian (SAS) AF: 0.660 AC: 3180 AN: 4820

European-Finnish (FIN) AF: 0.581 AC: 6124 AN: 10548

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.512 AC: 34769 AN: 67968

Other (OTH) AF: 0.535 AC: 1130 AN: 2112

Alfa AF: 0.519 Hom.: 4737

Bravo AF: 0.519

Asia WGS AF: 0.665 AC: 2314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.83
DANN	Benign	0.48
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs992670; hg19: chr9-123781770; COSMIC: COSV56325446;