rs3116494

Variant names:

• chr2-203727298-G-A
• rs3116494
• NM_006139.4:c.409+309G>A

Variant summary

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

The NM_006139.4(CD28):​c.409+309G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,080 control chromosomes in the GnomAD database, including 44,274 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 0.76 (44274 hom., cov: 30)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 29 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: ClinGen, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 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.409+309G>A		intron	N/A	NP_006130.1	P10747-1
	CD28	NM_001410981.1		c.451+309G>A		intron	N/A	NP_001397910.1	P10747-7
	CD28	NM_001243077.2		c.118+600G>A		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.409+309G>A		intron	N/A	ENSP00000324890.7	P10747-1
	CD28	ENST00000458610.6	TSL:1	c.451+309G>A		intron	N/A	ENSP00000393648.2	P10747-7
	CD28	ENST00000374481.8	TSL:1	c.53-2350G>A		intron	N/A	ENSP00000363605.4	P10747-2

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115745 AN: 151962 Hom.: 44236 Cov.: 30

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.762 AC: 115836 AN: 152080 Hom.: 44274 Cov.: 30 AF XY: 0.767 AC XY: 57076 AN XY: 74370

African (AFR) AF: 0.765 AC: 31729 AN: 41468

American (AMR) AF: 0.739 AC: 11297 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2344 AN: 3468

East Asian (EAS) AF: 0.920 AC: 4764 AN: 5176

South Asian (SAS) AF: 0.909 AC: 4381 AN: 4820

European-Finnish (FIN) AF: 0.817 AC: 8650 AN: 10582

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50356 AN: 67976

Other (OTH) AF: 0.742 AC: 1564 AN: 2108

Alfa AF: 0.753 Hom.: 16329

Bravo AF: 0.754

Asia WGS AF: 0.878 AC: 3050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.8
DANN	Benign	0.84
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3116494;

hg19: chr2-204592021;