NM_005214.5:c.*530_*571delATATATATATATATATATATATATATATATATATATATATAT

Variant names:

• chr2-203873327-CATATATATATATATATATATATATATATATATATATATATAT-C
• rs60872763
• NM_005214.5:c.*530_*571delATATATATATATATATATATATATATATATATATATATATAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005214.5(CTLA4):​c.*530_*571delATATATATATATATATATATATATATATATATATATATATAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 184,200 control chromosomes in the GnomAD database, including 33,300 homozygotes. 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. The gene CTLA4 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.45 (12373 hom., cov: 0)
  • Exomes 𝑓: 0.83 (20927 hom.)
• Consequence: CTLA4 NM_005214.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 3 publications found

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: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Specifications for CTLA4 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005214.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTLA4	NM_005214.5	MANE Select	c.*530_*571delATATATATATATATATATATATATATATATATATATATATAT		3_prime_UTR	Exon 4 of 4	NP_005205.2
	CTLA4	NM_001037631.3		c.*567_*608delATATATATATATATATATATATATATATATATATATATATAT		3_prime_UTR	Exon 3 of 3	NP_001032720.1	P16410-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTLA4	ENST00000648405.2	MANE Select	c.*530_*571delATATATATATATATATATATATATATATATATATATATATAT		3_prime_UTR	Exon 4 of 4	ENSP00000497102.1	P16410-1
	CTLA4	ENST00000696479.1		c.*530_*571delATATATATATATATATATATATATATATATATATATATATAT		3_prime_UTR	Exon 5 of 5	ENSP00000512655.1	A0A8Q3SIR7
	CTLA4	ENST00000696049.1		c.*516_*557delATATATATATATATATATATATATATATATATATATATATAT		downstream_gene	N/A	ENSP00000512353.1	A0A8Q3WKZ2

Frequencies

GnomAD3 genomes AF: 0.453 AC: 55768 AN: 122980 Hom.: 12371 Cov.: 0

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.625

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.509

GnomAD4 exome AF: 0.831 AC: 50904 AN: 61230 Hom.: 20927 AF XY: 0.830 AC XY: 25624 AN XY: 30884

African (AFR) AF: 0.722 AC: 864 AN: 1196

American (AMR) AF: 0.811 AC: 1624 AN: 2002

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2810 AN: 3314

East Asian (EAS) AF: 0.671 AC: 3259 AN: 4860

South Asian (SAS) AF: 0.882 AC: 743 AN: 842

European-Finnish (FIN) AF: 0.897 AC: 1287 AN: 1434

Middle Eastern (MID) AF: 0.863 AC: 373 AN: 432

European-Non Finnish (NFE) AF: 0.848 AC: 36209 AN: 42686

Other (OTH) AF: 0.837 AC: 3735 AN: 4464

GnomAD4 genome AF: 0.453 AC: 55760 AN: 122970 Hom.: 12373 Cov.: 0 AF XY: 0.461 AC XY: 27026 AN XY: 58656

African (AFR) AF: 0.309 AC: 9202 AN: 29798

American (AMR) AF: 0.492 AC: 6104 AN: 12394

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1742 AN: 3210

East Asian (EAS) AF: 0.295 AC: 1253 AN: 4244

South Asian (SAS) AF: 0.654 AC: 2845 AN: 4348

European-Finnish (FIN) AF: 0.537 AC: 3156 AN: 5872

Middle Eastern (MID) AF: 0.616 AC: 149 AN: 242

European-Non Finnish (NFE) AF: 0.498 AC: 30053 AN: 60310

Other (OTH) AF: 0.511 AC: 896 AN: 1752

Alfa AF: 0.393 Hom.: 380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs60872763; hg19: chr2-204738050;