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GeneBe

rs5742909

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000696479.1(CTLA4):c.48-294C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 152,272 control chromosomes in the GnomAD database, including 459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.068 ( 459 hom., cov: 33)

Consequence

CTLA4
ENST00000696479.1 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.123
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
Variant 2-203867624-C-T is Benign according to our data. Variant chr2-203867624-C-T is described in ClinVar as [Benign]. Clinvar id is 1168343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CTLA4ENST00000696479.1 linkuse as main transcriptc.48-294C>T intron_variant

Frequencies

GnomAD3 genomes
AF:
0.0683
AC:
10389
AN:
152154
Hom.:
458
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0160
Gnomad AMI
AF:
0.0429
Gnomad AMR
AF:
0.0698
Gnomad ASJ
AF:
0.0919
Gnomad EAS
AF:
0.108
Gnomad SAS
AF:
0.0402
Gnomad FIN
AF:
0.0967
Gnomad MID
AF:
0.0791
Gnomad NFE
AF:
0.0933
Gnomad OTH
AF:
0.0717
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0682
AC:
10386
AN:
152272
Hom.:
459
Cov.:
33
AF XY:
0.0679
AC XY:
5051
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0160
Gnomad4 AMR
AF:
0.0698
Gnomad4 ASJ
AF:
0.0919
Gnomad4 EAS
AF:
0.108
Gnomad4 SAS
AF:
0.0404
Gnomad4 FIN
AF:
0.0967
Gnomad4 NFE
AF:
0.0933
Gnomad4 OTH
AF:
0.0714
Alfa
AF:
0.0824
Hom.:
176
Bravo
AF:
0.0653
Asia WGS
AF:
0.0640
AC:
223
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 19, 2023- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 11, 2018This variant is associated with the following publications: (PMID: 21387262, 17341658, 16297665, 11426323, 12058260, 20732370, 18396212, 19913589, 11327371, 24298899, 23756164, 26051683) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.25
Cadd
Benign
15
Dann
Benign
0.60

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs5742909; hg19: chr2-204732347; API