rs831625

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000611.6(CD59):​c.-18-2427G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000992 in 151,206 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000099 ( 0 hom., cov: 29)

Consequence

CD59
NM_000611.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18
Variant links:
Genes affected
CD59 (HGNC:1689): (CD59 molecule (CD59 blood group)) This gene encodes a cell surface glycoprotein that regulates complement-mediated cell lysis, and it is involved in lymphocyte signal transduction. This protein is a potent inhibitor of the complement membrane attack complex, whereby it binds complement C8 and/or C9 during the assembly of this complex, thereby inhibiting the incorporation of multiple copies of C9 into the complex, which is necessary for osmolytic pore formation. This protein also plays a role in signal transduction pathways in the activation of T cells. Mutations in this gene cause CD59 deficiency, a disease resulting in hemolytic anemia and thrombosis, and which causes cerebral infarction. Multiple alternatively spliced transcript variants, which encode the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CD59NM_000611.6 linkuse as main transcriptc.-18-2427G>T intron_variant ENST00000642928.2 NP_000602.1
CD59NM_203329.3 linkuse as main transcriptc.-18-2427G>T intron_variant NP_976074.1
CD59NM_203330.2 linkuse as main transcriptc.-18-2427G>T intron_variant NP_976075.1
CD59NM_203331.3 linkuse as main transcriptc.-18-2427G>T intron_variant NP_976076.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CD59ENST00000642928.2 linkuse as main transcriptc.-18-2427G>T intron_variant NM_000611.6 ENSP00000494884 P1P13987-1

Frequencies

GnomAD3 genomes
AF:
0.0000992
AC:
15
AN:
151206
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.000267
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000198
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000480
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0000992
AC:
15
AN:
151206
Hom.:
0
Cov.:
29
AF XY:
0.0000813
AC XY:
6
AN XY:
73798
show subpopulations
Gnomad4 AFR
AF:
0.000267
Gnomad4 AMR
AF:
0.000198
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000480

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.073
DANN
Benign
0.18

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: rs831625; hg19: chr11-33746436; API