NM_006139.4:c.534+1102A>G

Variant names:

• chr2-203730874-A-G
• rs12693993
• NM_006139.4:c.534+1102A>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.534+1102A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 152,062 control chromosomes in the GnomAD database, including 29,867 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 0.62 (29867 hom., cov: 32)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• 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: 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 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+1102A>G		intron	N/A	NP_006130.1	P10747-1
	CD28	NM_001410981.1		c.576+1102A>G		intron	N/A	NP_001397910.1	P10747-7
	CD28	NM_001243077.2		c.243+1102A>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.534+1102A>G		intron	N/A	ENSP00000324890.7	P10747-1
	CD28	ENST00000458610.6	TSL:1	c.576+1102A>G		intron	N/A	ENSP00000393648.2	P10747-7
	CD28	ENST00000374481.8	TSL:1	c.177+1102A>G		intron	N/A	ENSP00000363605.4	P10747-2

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94261 AN: 151944 Hom.: 29832 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.620 AC: 94348 AN: 152062 Hom.: 29867 Cov.: 32 AF XY: 0.621 AC XY: 46148 AN XY: 74306

African (AFR) AF: 0.691 AC: 28668 AN: 41480

American (AMR) AF: 0.616 AC: 9427 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2373 AN: 3468

East Asian (EAS) AF: 0.863 AC: 4467 AN: 5174

South Asian (SAS) AF: 0.747 AC: 3592 AN: 4808

European-Finnish (FIN) AF: 0.531 AC: 5604 AN: 10560

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38214 AN: 67962

Other (OTH) AF: 0.634 AC: 1340 AN: 2114

Alfa AF: 0.583 Hom.: 15061

Bravo AF: 0.631

Asia WGS AF: 0.780 AC: 2715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.36
PhyloP100		-0.073
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: rs12693993; hg19: chr2-204595597;