rs3116496

Variant names:

• chr2-203729789-T-C
• rs3116496
• NM_006139.4:c.534+17T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006139.4(CD28):​c.534+17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,607,574 control chromosomes in the GnomAD database, including 22,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1696 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21283 hom.)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.91
• Publications: 80 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 2-203729789-T-C is Benign according to our data. Variant chr2-203729789-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 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.534+17T>C		intron	N/A	NP_006130.1	P10747-1
	CD28	NM_001410981.1		c.576+17T>C		intron	N/A	NP_001397910.1	P10747-7
	CD28	NM_001243077.2		c.243+17T>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.534+17T>C		intron	N/A	ENSP00000324890.7	P10747-1
	CD28	ENST00000458610.6	TSL:1	c.576+17T>C		intron	N/A	ENSP00000393648.2	P10747-7
	CD28	ENST00000374481.8	TSL:1	c.177+17T>C		intron	N/A	ENSP00000363605.4	P10747-2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20857 AN: 152086 Hom.: 1690 Cov.: 32

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.0749

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.161

GnomAD2 exomes AF: 0.147 AC: 35989 AN: 244856 AF XY: 0.148

Gnomad AFR exome AF: 0.0520

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.266

Gnomad EAS exome AF: 0.101

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.165 AC: 240455 AN: 1455372 Hom.: 21283 Cov.: 31 AF XY: 0.164 AC XY: 118819 AN XY: 723782

African (AFR) AF: 0.0514 AC: 1699 AN: 33046

American (AMR) AF: 0.110 AC: 4751 AN: 43320

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 6867 AN: 25872

East Asian (EAS) AF: 0.0823 AC: 3265 AN: 39658

South Asian (SAS) AF: 0.0898 AC: 7616 AN: 84788

European-Finnish (FIN) AF: 0.139 AC: 7391 AN: 53346

Middle Eastern (MID) AF: 0.228 AC: 1307 AN: 5726

European-Non Finnish (NFE) AF: 0.178 AC: 197882 AN: 1109432

Other (OTH) AF: 0.161 AC: 9677 AN: 60184

GnomAD4 genome AF: 0.137 AC: 20870 AN: 152202 Hom.: 1696 Cov.: 32 AF XY: 0.134 AC XY: 9932 AN XY: 74396

African (AFR) AF: 0.0553 AC: 2298 AN: 41548

American (AMR) AF: 0.123 AC: 1881 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 944 AN: 3468

East Asian (EAS) AF: 0.0965 AC: 500 AN: 5180

South Asian (SAS) AF: 0.0750 AC: 362 AN: 4824

European-Finnish (FIN) AF: 0.145 AC: 1533 AN: 10572

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12665 AN: 68006

Other (OTH) AF: 0.166 AC: 349 AN: 2108

Alfa AF: 0.177 Hom.: 4424

Bravo AF: 0.135

Asia WGS AF: 0.0960 AC: 337 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.4
DANN	Benign	0.81
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3116496; hg19: chr2-204594512; COSMIC: COSV60730736;