Variant 9-120963693-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001735.3(C5):c.4266G>A(p.Ala1422=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,613,500 control chromosomes in the GnomAD database, including 2,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 888 hom., cov: 32)

Exomes 𝑓: 0.025 ( 2035 hom. )

Consequence

C5
NM_001735.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.648

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 9-120963693-C-T is Benign according to our data. Variant chr9-120963693-C-T is described in ClinVar as [Benign]. Clinvar id is 1167627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.648 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C5	NM_001735.3 linkuse as main transcript	c.4266G>A	p.Ala1422=	synonymous_variant	34/41	ENST00000223642.3
C5	NM_001317163.2 linkuse as main transcript	c.4284G>A	p.Ala1428=	synonymous_variant	34/41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C5	ENST00000223642.3 linkuse as main transcript	c.4266G>A	p.Ala1422=	synonymous_variant	34/41	1	NM_001735.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0711

AC:

10809

AN:

151976

Hom.:

884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0317

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.0442

Gnomad FIN

AF:

0.0215

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0155

Gnomad OTH

AF:

0.0578

GnomAD3 exomes

AF:

0.0450

AC:

11301

AN:

251344

Hom.:

758

AF XY:

0.0417

AC XY:

5658

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.0289

Gnomad ASJ exome

AF:

0.0200

Gnomad EAS exome

AF:

0.183

Gnomad SAS exome

AF:

0.0385

Gnomad FIN exome

AF:

0.0253

Gnomad NFE exome

AF:

0.0142

Gnomad OTH exome

AF:

0.0308

GnomAD4 exome

AF:

0.0249

AC:

36327

AN:

1461406

Hom.:

2035

Cov.:

AF XY:

0.0251

AC XY:

18282

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.0295

Gnomad4 ASJ exome

AF:

0.0186

Gnomad4 EAS exome

AF:

0.215

Gnomad4 SAS exome

AF:

0.0403

Gnomad4 FIN exome

AF:

0.0271

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.0399

GnomAD4 genome

AF:

0.0713

AC:

10838

AN:

152094

Hom.:

888

Cov.:

AF XY:

0.0712

AC XY:

5292

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.0315

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.192

Gnomad4 SAS

AF:

0.0434

Gnomad4 FIN

AF:

0.0215

Gnomad4 NFE

AF:

0.0155

Gnomad4 OTH

AF:

0.0568

Alfa

AF:

0.0407

Hom.:

244

Bravo

AF:

0.0766

Asia WGS

AF:

0.113

AC:

391

AN:

3478

EpiCase

AF:

0.0139

EpiControl

AF:

0.0123

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

C5-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

6.6

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over