rs3181113

Variant names:

• chr2-203737187-G-T
• rs3181113
• NM_006139.4:c.*2275G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 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 -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 rank	MANE	Protein	UniProt
CD28	NM_006139.4	c.*2275G>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000324106.9	NP_006130.1
CD28	NM_001410981.1	c.*2275G>T		3_prime_UTR_variant	Exon 4 of 4		NP_001397910.1
CD28	NM_001243077.2	c.*2275G>T		3_prime_UTR_variant	Exon 4 of 4		NP_001230006.1
CD28	NM_001243078.2	c.*2275G>T		3_prime_UTR_variant	Exon 3 of 3		NP_001230007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD28	ENST00000324106.9	c.*2275G>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_006139.4	ENSP00000324890.7
CD28	ENST00000374481.8	c.*2275G>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000363605.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.102 AC: 4232 AN: 41496

American (AMR) AF: 0.151 AC: 2310 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3472

East Asian (EAS) AF: 0.490 AC: 2518 AN: 5144

South Asian (SAS) AF: 0.0750 AC: 361 AN: 4814

European-Finnish (FIN) AF: 0.0585 AC: 620 AN: 10602

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0416 AC: 2832 AN: 68010

Other (OTH) AF: 0.0824 AC: 174 AN: 2112

Alfa AF: 0.0592 Hom.: 2319

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
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3181113; hg19: chr2-204601910;