rs25681

Positions:

chr9-121017727-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001735.3(C5):c.1632C>T(p.Tyr544=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,611,088 control chromosomes in the GnomAD database, including 166,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 12470 hom., cov: 31)

Exomes 𝑓: 0.45 ( 153540 hom. )

Consequence

C5
NM_001735.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.50

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 9-121017727-G-A is Benign according to our data. Variant chr9-121017727-G-A is described in ClinVar as [Benign]. Clinvar id is 402455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-121017727-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
C5	NM_001735.3 linkuse as main transcript	c.1632C>T	p.Tyr544=	synonymous_variant	13/41	ENST00000223642.3	NP_001726.2
C5	NM_001317163.2 linkuse as main transcript	c.1650C>T	p.Tyr550=	synonymous_variant	13/41		NP_001304092.1
C5	NM_001317164.2 linkuse as main transcript	c.1632C>T	p.Tyr544=	synonymous_variant	13/21		NP_001304093.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000223642.3 linkuse as main transcript	c.1632C>T	p.Tyr544=	synonymous_variant	13/41	1	NM_001735.3	ENSP00000223642	P1

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55249

AN:

151880

Hom.:

12457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0853

Gnomad AMI

AF:

0.643

Gnomad AMR

AF:

0.491

Gnomad ASJ

AF:

0.521

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.623

Gnomad FIN

AF:

0.509

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.436

Gnomad OTH

AF:

0.408

GnomAD3 exomes

AF:

0.470

AC:

118062

AN:

251256

Hom.:

29808

AF XY:

0.482

AC XY:

65476

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.0729

Gnomad AMR exome

AF:

0.547

Gnomad ASJ exome

AF:

0.517

Gnomad EAS exome

AF:

0.560

Gnomad SAS exome

AF:

0.628

Gnomad FIN exome

AF:

0.489

Gnomad NFE exome

AF:

0.438

Gnomad OTH exome

AF:

0.471

GnomAD4 exome

AF:

0.451

AC:

657998

AN:

1459090

Hom.:

153540

Cov.:

AF XY:

0.457

AC XY:

332121

AN XY:

725974

show subpopulations

Gnomad4 AFR exome

AF:

0.0713

Gnomad4 AMR exome

AF:

0.542

Gnomad4 ASJ exome

AF:

0.512

Gnomad4 EAS exome

AF:

0.533

Gnomad4 SAS exome

AF:

0.629

Gnomad4 FIN exome

AF:

0.485

Gnomad4 NFE exome

AF:

0.439

Gnomad4 OTH exome

AF:

0.447

GnomAD4 genome

AF:

0.364

AC:

55262

AN:

151998

Hom.:

12470

Cov.:

AF XY:

0.374

AC XY:

27771

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0850

Gnomad4 AMR

AF:

0.492

Gnomad4 ASJ

AF:

0.521

Gnomad4 EAS

AF:

0.559

Gnomad4 SAS

AF:

0.625

Gnomad4 FIN

AF:

0.509

Gnomad4 NFE

AF:

0.435

Gnomad4 OTH

AF:

0.409

Alfa

AF:

0.409

Hom.:

10794

Bravo

AF:

0.350

Asia WGS

AF:

0.531

AC:

1846

AN:

3478

EpiCase

AF:

0.446

EpiControl

AF:

0.441

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 08, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.26

Position offset: -11

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