11-33724890-C-G

Variant names:

• chr11-33724890-C-G
• rs831625
• NM_000611.6:c.-18-2427G>C

Variant summary

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

The NM_000611.6(CD59):​c.-18-2427G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 151,274 control chromosomes in the GnomAD database, including 37,617 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 0.69 (37617 hom., cov: 29)
• Consequence: CD59 NM_000611.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD59	NM_000611.6	c.-18-2427G>C		intron_variant	Intron 1 of 3	ENST00000642928.2	NP_000602.1
CD59	NM_203329.3	c.-18-2427G>C		intron_variant	Intron 2 of 4		NP_976074.1
CD59	NM_203330.2	c.-18-2427G>C		intron_variant	Intron 3 of 5		NP_976075.1
CD59	NM_203331.3	c.-18-2427G>C		intron_variant	Intron 2 of 4		NP_976076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD59	ENST00000642928.2	c.-18-2427G>C		intron_variant	Intron 1 of 3		NM_000611.6	ENSP00000494884.1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104494 AN: 151154 Hom.: 37545 Cov.: 29

Gnomad AFR AF: 0.914

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.674

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

GnomAD4 genome AF: 0.692 AC: 104615 AN: 151274 Hom.: 37617 Cov.: 29 AF XY: 0.686 AC XY: 50686 AN XY: 73904

Gnomad4 AFR AF: 0.914

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.677

Alfa AF: 0.528 Hom.: 1428

Bravo AF: 0.689

Asia WGS AF: 0.630 AC: 2191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.079
DANN	Benign	0.40

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: rs831625; hg19: chr11-33746436;