NM_006139.4:c.52+4480A>G

Variant names:

• chr2-203711228-A-G
• rs1181388
• NM_006139.4:c.52+4480A>G

Variant summary

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

The NM_006139.4(CD28):​c.52+4480A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 152,120 control chromosomes in the GnomAD database, including 49,419 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 0.80 (49419 hom., cov: 31)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.861 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.52+4480A>G		intron	N/A	NP_006130.1	P10747-1
	CD28	NM_001410981.1		c.94+4611A>G		intron	N/A	NP_001397910.1	P10747-7
	CD28	NM_001243077.2		c.52+4480A>G		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.52+4480A>G		intron	N/A	ENSP00000324890.7	P10747-1
	CD28	ENST00000458610.6	TSL:1	c.94+4611A>G		intron	N/A	ENSP00000393648.2	P10747-7
	CD28	ENST00000374481.8	TSL:1	c.52+4480A>G		intron	N/A	ENSP00000363605.4	P10747-2

Frequencies

GnomAD3 genomes AF: 0.802 AC: 121902 AN: 152000 Hom.: 49407 Cov.: 31

Gnomad AFR AF: 0.723

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.802 AC: 121957 AN: 152120 Hom.: 49419 Cov.: 31 AF XY: 0.801 AC XY: 59549 AN XY: 74366

African (AFR) AF: 0.722 AC: 29944 AN: 41462

American (AMR) AF: 0.795 AC: 12140 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3123 AN: 3472

East Asian (EAS) AF: 0.481 AC: 2482 AN: 5156

South Asian (SAS) AF: 0.883 AC: 4257 AN: 4822

European-Finnish (FIN) AF: 0.861 AC: 9124 AN: 10596

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.856 AC: 58206 AN: 68012

Other (OTH) AF: 0.806 AC: 1705 AN: 2116

Alfa AF: 0.835 Hom.: 64761

Bravo AF: 0.788

Asia WGS AF: 0.719 AC: 2500 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	2.7
DANN	Benign	0.79
PhyloP100		0.091
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: rs1181388; hg19: chr2-204575951;