rs3181113

chr2-203737187-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006139.4(CD28):c.*2275G>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 0.0865 in 152,146 control chromosomes in the GnomAD database, including 1,146 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 0.087 (1146 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CD28 NM_006139.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD28	NM_006139.4	c.*2275G>T		3_prime_UTR_variant	4/4	ENST00000324106.9
CD28	NM_001243077.2	c.*2275G>T		3_prime_UTR_variant	4/4
CD28	NM_001243078.2	c.*2275G>T		3_prime_UTR_variant	3/3
CD28	NM_001410981.1	c.*2275G>T		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD28	ENST00000324106.9	c.*2275G>T		3_prime_UTR_variant	4/4	1	NM_006139.4	P1
CD28	ENST00000374481.7	c.*2275G>T		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.0865 AC: 13152 AN: 152028 Hom.: 1148 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.0585

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0842

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0865 AC: 13163 AN: 152146 Hom.: 1146 Cov.: 32 AF XY: 0.0916 AC XY: 6814 AN XY: 74382

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.0750

Gnomad4 FIN AF: 0.0585

Gnomad4 NFE AF: 0.0416

Gnomad4 OTH AF: 0.0824

Alfa AF: 0.0539 Hom.: 856

Bravo AF: 0.0987

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	1.8
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3181113; hg19: chr2-204601910;