dbSNP rs11585: CD59:c.*3967C>T (chr11-33706159-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.160

Publications

10 publications found

Variant links:

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 links:

ENSG00000284969 (HGNC:):

ENSG00000284969 links:

C11orf91 (HGNC:34444): (chromosome 11 open reading frame 91)

C11orf91 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CD59	NM_000611.6 link	c.*3967C>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000642928.2	NP_000602.1	P13987-1Q6FHM9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD59	ENST00000642928.2 link	c.*3967C>T		3_prime_UTR_variant	Exon 4 of 4		NM_000611.6	ENSP00000494884.1		P13987-1
ENSG00000284969	ENST00000534312.5 link	c.307+4047C>T		intron_variant	Intron 3 of 3	3		ENSP00000432362.1

Frequencies

GnomAD3 genomes

AF:

0.0994

AC:

15096

AN:

151878

Hom.:

988

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.250

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0994

AC:

15111

AN:

151994

Hom.:

992

Cov.:

AF XY:

0.0969

AC XY:

7203

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.171

AC:

7097

AN:

41428

American (AMR)

AF:

0.0525

AC:

801

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0570

AC:

198

AN:

3472

East Asian (EAS)

AF:

0.212

AC:

1093

AN:

5162

South Asian (SAS)

AF:

0.0898

AC:

431

AN:

4802

European-Finnish (FIN)

AF:

0.0405

AC:

428

AN:

10562

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0705

AC:

4795

AN:

67982

Other (OTH)

AF:

0.106

AC:

225

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

687

1374

2060

2747

3434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

166

332

498

664

830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0758

Hom.:

850

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

(source)

DANN

Benign

0.41

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over