rs831628

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD59	NM_000611.6	c.-18-836C>G		intron_variant	Intron 1 of 3	ENST00000642928.2	NP_000602.1
CD59	NM_203329.3	c.-18-836C>G		intron_variant	Intron 2 of 4		NP_976074.1
CD59	NM_203330.2	c.-18-836C>G		intron_variant	Intron 3 of 5		NP_976075.1
CD59	NM_203331.3	c.-18-836C>G		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.-18-836C>G		intron_variant	Intron 1 of 3		NM_000611.6	ENSP00000494884.1

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

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.199

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	9.3
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs831628; hg19: chr11-33744845;