chr11-33724890-C-G

Variant names:

• chr11-33724890-C-G
• rs831625
• NM_000611.6:c.-18-2427G>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.-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
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.914 AC: 37813 AN: 41384

American (AMR) AF: 0.541 AC: 8214 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2108 AN: 3446

East Asian (EAS) AF: 0.564 AC: 2854 AN: 5058

South Asian (SAS) AF: 0.623 AC: 2965 AN: 4758

European-Finnish (FIN) AF: 0.644 AC: 6770 AN: 10514

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.617 AC: 41739 AN: 67634

Other (OTH) AF: 0.677 AC: 1424 AN: 2102

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
PhyloP100		-1.2
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: rs831625; hg19: chr11-33746436;