chr11-33725787-C-T

Variant names:

• chr11-33725787-C-T
• rs861256
• NM_000611.6:c.-18-3324G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000611.6(CD59):​c.-18-3324G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 151,930 control chromosomes in the GnomAD database, including 28,721 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 0.61 (28721 hom., cov: 31)
• Consequence: CD59 NM_000611.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 13 publications found

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]

CD59 Gene-Disease associations (from GenCC):

• primary CD59 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000611.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD59	NM_000611.6	MANE Select	c.-18-3324G>A		intron	N/A	NP_000602.1	Q6FHM9
	CD59	NM_203329.3		c.-18-3324G>A		intron	N/A	NP_976074.1	P13987-1
	CD59	NM_203330.2		c.-18-3324G>A		intron	N/A	NP_976075.1	P13987-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD59	ENST00000642928.2	MANE Select	c.-18-3324G>A		intron	N/A	ENSP00000494884.1	P13987-1
	CD59	ENST00000395850.9	TSL:1	c.-131-2758G>A		intron	N/A	ENSP00000379191.3	P13987-1
	CD59	ENST00000873801.1		c.-18-3324G>A		intron	N/A	ENSP00000543860.1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 92999 AN: 151812 Hom.: 28683 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.613 AC: 93083 AN: 151930 Hom.: 28721 Cov.: 31 AF XY: 0.608 AC XY: 45157 AN XY: 74228

African (AFR) AF: 0.664 AC: 27500 AN: 41434

American (AMR) AF: 0.500 AC: 7629 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2108 AN: 3468

East Asian (EAS) AF: 0.486 AC: 2502 AN: 5152

South Asian (SAS) AF: 0.599 AC: 2883 AN: 4814

European-Finnish (FIN) AF: 0.635 AC: 6698 AN: 10550

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41761 AN: 67952

Other (OTH) AF: 0.620 AC: 1304 AN: 2104

Alfa AF: 0.608 Hom.: 44624

Bravo AF: 0.604

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.95
DANN	Benign	0.65
PhyloP100		-0.041
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs861256; hg19: chr11-33747333;