chr11-33722708-T-C

Variant names:

• chr11-33722708-T-C
• rs41275166
• ENST00000415002.7:c.-263A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000415002.7(CD59):​c.-263A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,292,598 control chromosomes in the GnomAD database, including 328 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 0.015 (35 hom., cov: 32)
  • Exomes 𝑓: 0.020 (293 hom.)
• Consequence: CD59 ENST00000415002.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 2 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

ENSG00000284969 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0152 (2311/152280) while in subpopulation NFE AF = 0.0233 (1582/68010). AF 95% confidence interval is 0.0223. There are 35 homozygotes in GnomAd4. There are 1100 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD59	NM_000611.6	c.-18-245A>G		intron_variant	Intron 1 of 3	ENST00000642928.2	NP_000602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD59	ENST00000642928.2	c.-18-245A>G		intron_variant	Intron 1 of 3		NM_000611.6	ENSP00000494884.1

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2311 AN: 152162 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.00379

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.00750

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0217

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0233

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.0204 AC: 23297 AN: 1140318 Hom.: 293 Cov.: 26 AF XY: 0.0201 AC XY: 11035 AN XY: 549686

African (AFR) AF: 0.00295 AC: 73 AN: 24768

American (AMR) AF: 0.00872 AC: 151 AN: 17314

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 156 AN: 14234

East Asian (EAS) AF: 0.0000463 AC: 1 AN: 21596

South Asian (SAS) AF: 0.00411 AC: 254 AN: 61778

European-Finnish (FIN) AF: 0.0223 AC: 351 AN: 15734

Middle Eastern (MID) AF: 0.00308 AC: 9 AN: 2924

European-Non Finnish (NFE) AF: 0.0230 AC: 21592 AN: 937880

Other (OTH) AF: 0.0161 AC: 710 AN: 44090

GnomAD4 genome AF: 0.0152 AC: 2311 AN: 152280 Hom.: 35 Cov.: 32 AF XY: 0.0148 AC XY: 1100 AN XY: 74466

African (AFR) AF: 0.00378 AC: 157 AN: 41568

American (AMR) AF: 0.0120 AC: 184 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00750 AC: 26 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4824

European-Finnish (FIN) AF: 0.0217 AC: 230 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0233 AC: 1582 AN: 68010

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.0206 Hom.: 49

Bravo AF: 0.0148

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.74
PhyloP100		-1.2
PromoterAI		0.0041	Neutral
Mutation Taster		=300/0	polymorphism

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: rs41275166; hg19: chr11-33744254;