rs831628

Variant names:

• chr11-33723299-G-C
• rs831628
• NM_000611.6:c.-18-836C>G

Variant summary

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

The NM_000611.6(CD59):​c.-18-836C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,014 control chromosomes in the GnomAD database, including 4,161 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 0.23 (4161 hom., cov: 32)
• Consequence: CD59 NM_000611.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.316 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.-18-836C>G		intron	N/A	NP_000602.1	Q6FHM9
	CD59	NM_203329.3		c.-18-836C>G		intron	N/A	NP_976074.1	P13987-1
	CD59	NM_203330.2		c.-18-836C>G		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.-18-836C>G		intron	N/A	ENSP00000494884.1	P13987-1
	CD59	ENST00000395850.9	TSL:1	c.-131-270C>G		intron	N/A	ENSP00000379191.3	P13987-1
	CD59	ENST00000873801.1		c.-18-836C>G		intron	N/A	ENSP00000543860.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34603 AN: 151894 Hom.: 4140 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.228 AC: 34660 AN: 152014 Hom.: 4161 Cov.: 32 AF XY: 0.232 AC XY: 17240 AN XY: 74306

African (AFR) AF: 0.254 AC: 10529 AN: 41454

American (AMR) AF: 0.199 AC: 3048 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 390 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1139 AN: 5156

South Asian (SAS) AF: 0.329 AC: 1583 AN: 4808

European-Finnish (FIN) AF: 0.278 AC: 2939 AN: 10566

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14346 AN: 67960

Other (OTH) AF: 0.199 AC: 421 AN: 2112

Alfa AF: 0.225 Hom.: 471

Bravo AF: 0.218

Asia WGS AF: 0.300 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.3
DANN	Benign	0.65
PhyloP100		1.9
PromoterAI		-0.13	Neutral
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: rs831628; hg19: chr11-33744845;