9-121008158-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001735.3(C5):​c.2348+250T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,014 control chromosomes in the GnomAD database, including 29,685 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 0.62 ( 29685 hom., cov: 32)

Consequence

C5
NM_001735.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.50
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
C5NM_001735.3 linkuse as main transcriptc.2348+250T>G intron_variant ENST00000223642.3
C5NM_001317163.2 linkuse as main transcriptc.2366+250T>G intron_variant
C5NM_001317164.2 linkuse as main transcriptc.2348+250T>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
C5ENST00000223642.3 linkuse as main transcriptc.2348+250T>G intron_variant 1 NM_001735.3 P1

Frequencies

GnomAD3 genomes
AF:
0.623
AC:
94621
AN:
151896
Hom.:
29645
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.614
Gnomad AMI
AF:
0.694
Gnomad AMR
AF:
0.622
Gnomad ASJ
AF:
0.632
Gnomad EAS
AF:
0.813
Gnomad SAS
AF:
0.753
Gnomad FIN
AF:
0.638
Gnomad MID
AF:
0.561
Gnomad NFE
AF:
0.602
Gnomad OTH
AF:
0.604
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.623
AC:
94718
AN:
152014
Hom.:
29685
Cov.:
32
AF XY:
0.627
AC XY:
46577
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.614
Gnomad4 AMR
AF:
0.622
Gnomad4 ASJ
AF:
0.632
Gnomad4 EAS
AF:
0.813
Gnomad4 SAS
AF:
0.753
Gnomad4 FIN
AF:
0.638
Gnomad4 NFE
AF:
0.602
Gnomad4 OTH
AF:
0.606
Alfa
AF:
0.612
Hom.:
50238
Bravo
AF:
0.620
Asia WGS
AF:
0.763
AC:
2650
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
0.10
DANN
Benign
0.31

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

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

Other links and lift over

dbSNP: rs2300932; hg19: chr9-123770436; API