ENST00000415002.7:c.-263A>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting 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. Variant has been reported in ClinVar as (no stars).

• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ENSG00000284969 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -9 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. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 35 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000415002.7. 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.-18-245A>G		intron	N/A	NP_000602.1	Q6FHM9
	CD59	NM_001127223.1		c.-263A>G		5_prime_UTR	Exon 1 of 3	NP_001120695.1	Q6FHM9
	CD59	NM_001127225.2		c.-156A>G		5_prime_UTR	Exon 1 of 4	NP_001120697.1	P13987-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD59	ENST00000415002.7	TSL:1	c.-263A>G		5_prime_UTR	Exon 1 of 3	ENSP00000404822.2	P13987-1
	CD59	ENST00000642928.2	MANE Select	c.-18-245A>G		intron	N/A	ENSP00000494884.1	P13987-1
	CD59	ENST00000395850.9	TSL:1	c.-19+209A>G		intron	N/A	ENSP00000379191.3	P13987-1

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 v4.9

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;