chr11-33720111-C-G

Variant names:

• chr11-33720111-C-G
• rs10501127
• NM_000611.6:c.67+2268G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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

ENSG00000284969 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.67+2268G>C		intron	N/A	NP_000602.1	Q6FHM9
	CD59	NM_001127223.1		c.67+2268G>C		intron	N/A	NP_001120695.1	Q6FHM9
	CD59	NM_001127225.2		c.67+2268G>C		intron	N/A	NP_001120697.1	P13987-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD59	ENST00000642928.2	MANE Select	c.67+2268G>C		intron	N/A	ENSP00000494884.1	P13987-1
	ENSG00000284969	ENST00000534312.5	TSL:3	c.67+2268G>C		intron	N/A	ENSP00000432362.1
	CD59	ENST00000395850.9	TSL:1	c.67+2268G>C		intron	N/A	ENSP00000379191.3	P13987-1

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

African (AFR) AF: 0.0521 AC: 2167 AN: 41558

American (AMR) AF: 0.0928 AC: 1419 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0822 AC: 285 AN: 3468

East Asian (EAS) AF: 0.0166 AC: 86 AN: 5184

South Asian (SAS) AF: 0.155 AC: 747 AN: 4818

European-Finnish (FIN) AF: 0.221 AC: 2337 AN: 10584

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11006 AN: 67986

Other (OTH) AF: 0.115 AC: 243 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.5
DANN	Benign	0.52
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10501127; hg19: chr11-33741657;