rs7031128

Variant names:

• chr9-121029658-C-A
• rs7031128
• NM_001735.3:c.758+739G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-121029658-C-A
• chr9-121029658-C-G
• chr9-121029658-C-T

Variant summary

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

The NM_001317163.2(C5):​c.776+739G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,054 control chromosomes in the GnomAD database, including 43,171 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 0.75 (43171 hom., cov: 32)
• Consequence: C5 NM_001317163.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317163.2. 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.758+739G>T		intron	N/A	NP_001726.2
	C5	NM_001317163.2		c.776+739G>T		intron	N/A	NP_001304092.1
	C5	NM_001317164.2		c.758+739G>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.758+739G>T		intron	N/A	ENSP00000223642.1
	C5	ENST00000696281.1		c.776+739G>T		intron	N/A	ENSP00000512521.1
	C5	ENST00000867873.1		c.758+739G>T		intron	N/A	ENSP00000537932.1

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113894 AN: 151936 Hom.: 43129 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.801

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.929

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.750 AC: 113994 AN: 152054 Hom.: 43171 Cov.: 32 AF XY: 0.751 AC XY: 55850 AN XY: 74318

African (AFR) AF: 0.652 AC: 27024 AN: 41450

American (AMR) AF: 0.814 AC: 12453 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2652 AN: 3468

East Asian (EAS) AF: 0.995 AC: 5157 AN: 5184

South Asian (SAS) AF: 0.929 AC: 4480 AN: 4822

European-Finnish (FIN) AF: 0.716 AC: 7533 AN: 10528

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.767 AC: 52122 AN: 67988

Other (OTH) AF: 0.767 AC: 1622 AN: 2114

Alfa AF: 0.768 Hom.: 139918

Bravo AF: 0.753

Asia WGS AF: 0.933 AC: 3243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.55
PhyloP100		-0.29
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: rs7031128; hg19: chr9-123791936;