rs10538602

Positions:

• chr11-33731325-CAT-C
• chr11-33731325-CAT-CATAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000611.6(CD59):​c.-19+5055_-19+5056del variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6327 hom., cov: 19)
  • Failed GnomAD Quality Control
• Consequence: CD59 NM_000611.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD59	NM_000611.6	c.-19+5055_-19+5056del		intron_variant		ENST00000642928.2
CD59	NM_203329.3	c.-19+2168_-19+2169del		intron_variant
CD59	NM_203330.2	c.-19+97_-19+98del		intron_variant
CD59	NM_203331.3	c.-19+97_-19+98del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD59	ENST00000642928.2	c.-19+5055_-19+5056del		intron_variant			NM_000611.6	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43059 AN: 151328 Hom.: 6325 Cov.: 19

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.328

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.284 AC: 43069 AN: 151440 Hom.: 6327 Cov.: 19 AF XY: 0.283 AC XY: 20933 AN XY: 73960

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.322

Alfa AF: 0.158 Hom.: 307

Bravo AF: 0.284

Asia WGS AF: 0.273 AC: 949 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs10538602; hg19: chr11-33752871;