chr9-121019860-C-T

Variant names:

• chr9-121019860-C-T
• rs2241004
• NM_001735.3:c.1506+116G>A

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+116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 692,742 control chromosomes in the GnomAD database, including 143,966 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 0.63 (30538 hom., cov: 32)
  • Exomes 𝑓: 0.65 (113428 hom.)
• Consequence: C5 NM_001735.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.705
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5	NM_001735.3	MANE Select	c.1506+116G>A		intron	N/A	NP_001726.2
	C5	NM_001317163.2		c.1524+116G>A		intron	N/A	NP_001304092.1	A0A8Q3SID6
	C5	NM_001317164.2		c.1506+116G>A		intron	N/A	NP_001304093.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C5	ENST00000223642.3	TSL:1 MANE Select	c.1506+116G>A		intron	N/A	ENSP00000223642.1	P01031
	C5	ENST00000696281.1		c.1524+116G>A		intron	N/A	ENSP00000512521.1	A0A8Q3SID6
	C5	ENST00000867873.1		c.1506+116G>A		intron	N/A	ENSP00000537932.1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96135 AN: 151900 Hom.: 30502 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.643

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.620

GnomAD4 exome AF: 0.645 AC: 348787 AN: 540724 Hom.: 113428 AF XY: 0.652 AC XY: 187657 AN XY: 288016

African (AFR) AF: 0.619 AC: 8738 AN: 14114

American (AMR) AF: 0.654 AC: 16660 AN: 25478

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 10725 AN: 17006

East Asian (EAS) AF: 0.749 AC: 23920 AN: 31920

South Asian (SAS) AF: 0.742 AC: 39669 AN: 53436

European-Finnish (FIN) AF: 0.629 AC: 26248 AN: 41698

Middle Eastern (MID) AF: 0.617 AC: 1400 AN: 2268

European-Non Finnish (NFE) AF: 0.623 AC: 202692 AN: 325564

Other (OTH) AF: 0.641 AC: 18735 AN: 29240

GnomAD4 genome AF: 0.633 AC: 96231 AN: 152018 Hom.: 30538 Cov.: 32 AF XY: 0.636 AC XY: 47245 AN XY: 74322

African (AFR) AF: 0.615 AC: 25518 AN: 41468

American (AMR) AF: 0.642 AC: 9809 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2202 AN: 3468

East Asian (EAS) AF: 0.777 AC: 4025 AN: 5182

South Asian (SAS) AF: 0.751 AC: 3627 AN: 4828

European-Finnish (FIN) AF: 0.643 AC: 6771 AN: 10534

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

European-Non Finnish (NFE) AF: 0.620 AC: 42159 AN: 67956

Other (OTH) AF: 0.620 AC: 1309 AN: 2112

Alfa AF: 0.630 Hom.: 7871

Bravo AF: 0.631

Asia WGS AF: 0.734 AC: 2551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.2
DANN	Benign	0.59
PhyloP100		-0.70
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: rs2241004; hg19: chr9-123782138;