11-33720111-C-G

Position:

• chr11-33720111-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000611.6(CD59):​c.67+2268G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,210 control chromosomes in the GnomAD database, including 1,438 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 0.12 (1438 hom., cov: 33)
• Consequence: CD59 NM_000611.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD59	NM_000611.6	c.67+2268G>C		intron_variant		ENST00000642928.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD59	ENST00000642928.2	c.67+2268G>C		intron_variant			NM_000611.6	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18512 AN: 152092 Hom.: 1425 Cov.: 33

Gnomad AFR AF: 0.0522

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.0931

Gnomad ASJ AF: 0.0822

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.104

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

GnomAD4 genome AF: 0.122 AC: 18535 AN: 152210 Hom.: 1438 Cov.: 33 AF XY: 0.124 AC XY: 9259 AN XY: 74414

Gnomad4 AFR AF: 0.0521

Gnomad4 AMR AF: 0.0928

Gnomad4 ASJ AF: 0.0822

Gnomad4 EAS AF: 0.0166

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0873 Hom.: 134

Bravo AF: 0.105

Asia WGS AF: 0.121 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.5
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs10501127; hg19: chr11-33741657;