rs3116494

chr2-203727298-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD28	NM_006139.4	c.409+309G>A		intron_variant		ENST00000324106.9
CD28	NM_001243077.2	c.118+600G>A		intron_variant
CD28	NM_001243078.2	c.53-2350G>A		intron_variant
CD28	NM_001410981.1	c.451+309G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD28	ENST00000324106.9	c.409+309G>A		intron_variant		1	NM_006139.4	P1
CD28	ENST00000374481.7	c.53-2350G>A		intron_variant		1
CD28	ENST00000458610.6	c.451+309G>A		intron_variant		1

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

Gnomad4 AFR AF: 0.765

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.676

Gnomad4 EAS AF: 0.920

Gnomad4 SAS AF: 0.909

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.742

Alfa AF: 0.750 Hom.: 9605

Bravo AF: 0.754

Asia WGS AF: 0.878 AC: 3050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	5.8
Dann	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs3116494; hg19: chr2-204592021;