rs11585

Positions:

• chr11-33706159-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000611.6(CD59):​c.*3967C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 152,004 control chromosomes in the GnomAD database, including 992 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 0.099 (992 hom., cov: 31)
  • Exomes 𝑓: 0.30 (0 hom.)
• Consequence: CD59 NM_000611.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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]

C11orf91 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD59	NM_000611.6	c.*3967C>T		3_prime_UTR_variant	4/4	ENST00000642928.2	NP_000602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD59	ENST00000642928.2	c.*3967C>T		3_prime_UTR_variant	4/4		NM_000611.6	ENSP00000494884	P1
CD59	ENST00000651785.1	c.*3967C>T		3_prime_UTR_variant	6/6			ENSP00000498879	P1
CD59	ENST00000652678.1	c.*3967C>T		3_prime_UTR_variant	4/4			ENSP00000498448	P1
CD59	ENST00000706436.1	c.*4116C>T		3_prime_UTR_variant	4/4			ENSP00000516379

Frequencies

GnomAD3 genomes AF: 0.0994 AC: 15096 AN: 151878 Hom.: 988 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.0570

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.0897

Gnomad FIN AF: 0.0405

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0705

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.300 AC: 3 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

Gnomad4 EAS exome AF: 0.250

Gnomad4 NFE exome AF: 0.333

GnomAD4 genome AF: 0.0994 AC: 15111 AN: 151994 Hom.: 992 Cov.: 31 AF XY: 0.0969 AC XY: 7203 AN XY: 74308

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0525

Gnomad4 ASJ AF: 0.0570

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.0898

Gnomad4 FIN AF: 0.0405

Gnomad4 NFE AF: 0.0705

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0734 Hom.: 607

Bravo AF: 0.104

Asia WGS AF: 0.142 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11585; hg19: chr11-33727705;