rs41258306

Variant names:

• chr9-120953825-T-C
• rs41258306
• NM_001735.3:c.4806A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-120953825-T-C
• chr9-120953825-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001735.3(C5):​c.4806A>G​(p.Lys1602Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 1,613,206 control chromosomes in the GnomAD database, including 3,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (308 hom., cov: 32)
  • Exomes 𝑓: 0.064 (3360 hom.)
• Consequence: C5 NM_001735.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0580

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]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 9-120953825-T-C is Benign according to our data. Variant chr9-120953825-T-C is described in ClinVar as [Benign]. Clinvar id is 402450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.058 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5	NM_001735.3	c.4806A>G	p.Lys1602Lys	synonymous_variant	Exon 40 of 41	ENST00000223642.3	NP_001726.2
C5	NM_001317163.2	c.4824A>G	p.Lys1608Lys	synonymous_variant	Exon 40 of 41		NP_001304092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5	ENST00000223642.3	c.4806A>G	p.Lys1602Lys	synonymous_variant	Exon 40 of 41	1	NM_001735.3	ENSP00000223642.1

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8825 AN: 152190 Hom.: 303 Cov.: 32

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.0628

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0650

Gnomad OTH AF: 0.0570

GnomAD2 exomes AF: 0.0571 AC: 14348 AN: 251378 AF XY: 0.0572

Gnomad AFR exome AF: 0.0642

Gnomad AMR exome AF: 0.0599

Gnomad ASJ exome AF: 0.0648

Gnomad EAS exome AF: 0.00109

Gnomad FIN exome AF: 0.0152

Gnomad NFE exome AF: 0.0686

Gnomad OTH exome AF: 0.0584

GnomAD4 exome AF: 0.0643 AC: 93873 AN: 1460898 Hom.: 3360 Cov.: 31 AF XY: 0.0645 AC XY: 46892 AN XY: 726806

Gnomad4 AFR exome AF: 0.0652 AC: 2180 AN: 33456

Gnomad4 AMR exome AF: 0.0592 AC: 2646 AN: 44724

Gnomad4 ASJ exome AF: 0.0620 AC: 1620 AN: 26132

Gnomad4 EAS exome AF: 0.000907 AC: 36 AN: 39684

Gnomad4 SAS exome AF: 0.0678 AC: 5845 AN: 86242

Gnomad4 FIN exome AF: 0.0168 AC: 898 AN: 53418

Gnomad4 NFE exome AF: 0.0688 AC: 76453 AN: 1111108

Gnomad4 Remaining exome AF: 0.0635 AC: 3831 AN: 60368

GnomAD4 genome AF: 0.0581 AC: 8842 AN: 152308 Hom.: 308 Cov.: 32 AF XY: 0.0559 AC XY: 4160 AN XY: 74484

Gnomad4 AFR AF: 0.0630 AC: 0.0630054 AN: 0.0630054

Gnomad4 AMR AF: 0.0592 AC: 0.0592234 AN: 0.0592234

Gnomad4 ASJ AF: 0.0628 AC: 0.062788 AN: 0.062788

Gnomad4 EAS AF: 0.00116 AC: 0.00115518 AN: 0.00115518

Gnomad4 SAS AF: 0.0736 AC: 0.0735904 AN: 0.0735904

Gnomad4 FIN AF: 0.0132 AC: 0.0131777 AN: 0.0131777

Gnomad4 NFE AF: 0.0650 AC: 0.0650173 AN: 0.0650173

Gnomad4 OTH AF: 0.0573 AC: 0.057346 AN: 0.057346

Alfa AF: 0.0670 Hom.: 550

Bravo AF: 0.0616

Asia WGS AF: 0.0420 AC: 147 AN: 3478

EpiCase AF: 0.0703

EpiControl AF: 0.0713

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.0
DANN	Benign	0.53
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

Publications

LitVar

Other links and lift over

dbSNP: rs41258306; hg19: chr9-123716103;