rs3116486

Variant names:

• chr2-203720779-T-C
• rs3116486
• NM_006139.4:c.53-5854T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006139.4(CD28):​c.53-5854T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,252 control chromosomes in the GnomAD database, including 1,765 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 0.14 (1765 hom., cov: 32)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770
• Publications: 6 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: MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006139.4. 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
	CD28	NM_006139.4	MANE Select	c.53-5854T>C		intron	N/A	NP_006130.1	P10747-1
	CD28	NM_001410981.1		c.95-5854T>C		intron	N/A	NP_001397910.1	P10747-7
	CD28	NM_001243077.2		c.53-5854T>C		intron	N/A	NP_001230006.1	P10747-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD28	ENST00000324106.9	TSL:1 MANE Select	c.53-5854T>C		intron	N/A	ENSP00000324890.7	P10747-1
	CD28	ENST00000458610.6	TSL:1	c.95-5854T>C		intron	N/A	ENSP00000393648.2	P10747-7
	CD28	ENST00000374481.8	TSL:1	c.53-8869T>C		intron	N/A	ENSP00000363605.4	P10747-2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21950 AN: 152134 Hom.: 1764 Cov.: 32

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0709

Gnomad SAS AF: 0.0624

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.165

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.144 AC: 21960 AN: 152252 Hom.: 1765 Cov.: 32 AF XY: 0.141 AC XY: 10523 AN XY: 74428

African (AFR) AF: 0.0878 AC: 3649 AN: 41558

American (AMR) AF: 0.170 AC: 2595 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 944 AN: 3470

East Asian (EAS) AF: 0.0711 AC: 369 AN: 5192

South Asian (SAS) AF: 0.0624 AC: 301 AN: 4822

European-Finnish (FIN) AF: 0.126 AC: 1339 AN: 10598

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12072 AN: 68008

Other (OTH) AF: 0.169 AC: 358 AN: 2116

Alfa AF: 0.156 Hom.: 246

Bravo AF: 0.147

Asia WGS AF: 0.0810 AC: 286 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.7
DANN	Benign	0.90
PhyloP100		-0.77
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: rs3116486; hg19: chr2-204585502;