ENST00000458610.6:c.-198_-197insC

Variant names:

• chr2-203706326-T-TC
• rs56156157
• ENST00000458610.6:c.-198_-197insC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000458610.6(CD28):​c.-198_-197insC variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 559,698 control chromosomes in the GnomAD database, including 56 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (18 hom., cov: 31)
  • Exomes 𝑓: 0.010 (38 hom.)
• Consequence: CD28 ENST00000458610.6 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235
• Publications: 2 publications found

Genes affected

CD28 (HGNC:1653): (CD28 molecule) The protein encoded by this gene is essential for T-cell proliferation and survival, cytokine production, and T-helper type-2 development. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011]

CD28 Gene-Disease associations (from GenCC):

• immunodeficiency 123 with HPV-related verrucosis

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0131 (1990/151934) while in subpopulation AFR AF = 0.0191 (793/41440). AF 95% confidence interval is 0.018. There are 18 homozygotes in GnomAd4. There are 989 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000458610.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD28	NM_001410981.1		c.-198_-197insC		upstream_gene	N/A	NP_001397910.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD28	ENST00000458610.6	TSL:1	c.-198_-197insC		upstream_gene	N/A	ENSP00000393648.2
	CD28	ENST00000374481.8	TSL:1	c.-371_-370insC		upstream_gene	N/A	ENSP00000363605.4
	CD28	ENST00000718458.1		c.-198_-197insC		upstream_gene	N/A	ENSP00000520836.1

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1979 AN: 151816 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00635

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00962

Gnomad OTH AF: 0.0163

GnomAD4 exome AF: 0.0103 AC: 4203 AN: 407764 Hom.: 38 AF XY: 0.0106 AC XY: 2260 AN XY: 212972

African (AFR) AF: 0.0213 AC: 250 AN: 11742

American (AMR) AF: 0.0107 AC: 173 AN: 16126

Ashkenazi Jewish (ASJ) AF: 0.00775 AC: 100 AN: 12904

East Asian (EAS) AF: 0.000202 AC: 6 AN: 29768

South Asian (SAS) AF: 0.0165 AC: 567 AN: 34380

European-Finnish (FIN) AF: 0.0152 AC: 414 AN: 27276

Middle Eastern (MID) AF: 0.0352 AC: 64 AN: 1818

European-Non Finnish (NFE) AF: 0.00940 AC: 2344 AN: 249486

Other (OTH) AF: 0.0117 AC: 285 AN: 24264

GnomAD4 genome AF: 0.0131 AC: 1990 AN: 151934 Hom.: 18 Cov.: 31 AF XY: 0.0133 AC XY: 989 AN XY: 74232

African (AFR) AF: 0.0191 AC: 793 AN: 41440

American (AMR) AF: 0.0116 AC: 176 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00635 AC: 22 AN: 3464

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5152

South Asian (SAS) AF: 0.0135 AC: 65 AN: 4800

European-Finnish (FIN) AF: 0.0193 AC: 204 AN: 10562

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00962 AC: 654 AN: 67970

Other (OTH) AF: 0.0161 AC: 34 AN: 2106

Alfa AF: 0.0106 Hom.: 0

Bravo AF: 0.0129

Asia WGS AF: 0.00866 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs56156157; hg19: chr2-204571049;