2-203721314-C-G

Variant names:

• chr2-203721314-C-G
• rs3116487
• NM_006139.4:c.53-5319C>G

Variant summary

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

The ENST00000324106.9(CD28):​c.53-5319C>G 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 152,158 control chromosomes in the GnomAD database, including 1,756 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 (1756 hom., cov: 32)
• Consequence: CD28 ENST00000324106.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836
• Publications: 9 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=-0.87).
• 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: ENST00000324106.9. 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_006139.4	MANE Select	c.53-5319C>G		intron	N/A	NP_006130.1
	CD28	NM_001410981.1		c.95-5319C>G		intron	N/A	NP_001397910.1
	CD28	NM_001243077.2		c.53-5319C>G		intron	N/A	NP_001230006.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD28	ENST00000324106.9	TSL:1 MANE Select	c.53-5319C>G		intron	N/A	ENSP00000324890.7
	CD28	ENST00000458610.6	TSL:1	c.95-5319C>G		intron	N/A	ENSP00000393648.2
	CD28	ENST00000374481.8	TSL:1	c.53-8334C>G		intron	N/A	ENSP00000363605.4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21918 AN: 152040 Hom.: 1755 Cov.: 32

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0703

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.177

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: 21928 AN: 152158 Hom.: 1756 Cov.: 32 AF XY: 0.141 AC XY: 10516 AN XY: 74414

African (AFR) AF: 0.0876 AC: 3638 AN: 41516

American (AMR) AF: 0.170 AC: 2599 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3468

East Asian (EAS) AF: 0.0704 AC: 365 AN: 5182

South Asian (SAS) AF: 0.0622 AC: 300 AN: 4826

European-Finnish (FIN) AF: 0.126 AC: 1335 AN: 10568

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

European-Non Finnish (NFE) AF: 0.177 AC: 12055 AN: 67986

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

Alfa AF: 0.0701 Hom.: 94

Bravo AF: 0.147

Asia WGS AF: 0.0820 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.65
PhyloP100		-0.84
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: rs3116487; hg19: chr2-204586037;