GeneBe

rs60872763

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005214.5(CTLA4):​c.*526_*571delATATATATATATATATATATATATATATATATATATATATATATAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 183,326 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CTLA4
NM_005214.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.83

Publications

3 publications found
Variant links:
Genes affected
CTLA4 (HGNC:2505): (cytotoxic T-lymphocyte associated protein 4) This gene is a member of the immunoglobulin superfamily and encodes a protein which transmits an inhibitory signal to T cells. The protein contains a V domain, a transmembrane domain, and a cytoplasmic tail. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. The membrane-bound isoform functions as a homodimer interconnected by a disulfide bond, while the soluble isoform functions as a monomer. Mutations in this gene have been associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases. [provided by RefSeq, Jul 2008]
CTLA4 Gene-Disease associations (from GenCC):
  • autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
  • systemic lupus erythematosus
    Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CTLA4NM_005214.5 linkc.*526_*571delATATATATATATATATATATATATATATATATATATATATATATAT 3_prime_UTR_variant Exon 4 of 4 ENST00000648405.2 NP_005205.2 P16410-1
CTLA4NM_001037631.3 linkc.*563_*608delATATATATATATATATATATATATATATATATATATATATATATAT 3_prime_UTR_variant Exon 3 of 3 NP_001032720.1 P16410-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTLA4ENST00000648405.2 linkc.*526_*571delATATATATATATATATATATATATATATATATATATATATATATAT 3_prime_UTR_variant Exon 4 of 4 NM_005214.5 ENSP00000497102.1 P16410-1
CTLA4ENST00000696479.1 linkc.*526_*571delATATATATATATATATATATATATATATATATATATATATATATAT 3_prime_UTR_variant Exon 5 of 5 ENSP00000512655.1 A0A8Q3SIR7
CTLA4ENST00000696049.1 linkc.*516_*561delATATATATATATATATATATATATATATATATATATATATATATAT downstream_gene_variant ENSP00000512353.1 A0A8Q3WKZ2
CTLA4ENST00000427473.3 linkn.*238_*283delATATATATATATATATATATATATATATATATATATATATATATAT downstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
4
AN:
122106
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0000677
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000163
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000163
AC:
1
AN:
61220
Hom.:
0
AF XY:
0.0000324
AC XY:
1
AN XY:
30874
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
1196
American (AMR)
AF:
0.00
AC:
0
AN:
2002
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3310
East Asian (EAS)
AF:
0.000206
AC:
1
AN:
4856
South Asian (SAS)
AF:
0.00
AC:
0
AN:
842
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
1434
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
430
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
42686
Other (OTH)
AF:
0.00
AC:
0
AN:
4464
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000328
AC:
4
AN:
122106
Hom.:
0
Cov.:
0
AF XY:
0.0000172
AC XY:
1
AN XY:
58180
show subpopulations
African (AFR)
AF:
0.0000677
AC:
2
AN:
29540
American (AMR)
AF:
0.000163
AC:
2
AN:
12280
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3186
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4260
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4344
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
5808
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
252
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
59916
Other (OTH)
AF:
0.00
AC:
0
AN:
1722
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.638
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.8

Splicing

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

Publications

Other links and lift over

dbSNP: rs60872763; hg19: chr2-204738050; API