2-203714074-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006139.4(CD28):c.52+7326A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 152,006 control chromosomes in the GnomAD database, including 55,071 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 0.85 (55071 hom., cov: 28)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD28	NM_006139.4	c.52+7326A>G		intron_variant		ENST00000324106.9
CD28	NM_001243077.2	c.52+7326A>G		intron_variant
CD28	NM_001243078.2	c.52+7326A>G		intron_variant
CD28	NM_001410981.1	c.94+7457A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD28	ENST00000324106.9	c.52+7326A>G		intron_variant		1	NM_006139.4	P1
CD28	ENST00000374481.7	c.52+7326A>G		intron_variant		1
CD28	ENST00000458610.6	c.94+7457A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.849 AC: 128995 AN: 151886 Hom.: 55036 Cov.: 28

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.837

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.906

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.863

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.849 AC: 129088 AN: 152006 Hom.: 55071 Cov.: 28 AF XY: 0.848 AC XY: 62987 AN XY: 74290

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.906

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.897

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.866

Gnomad4 OTH AF: 0.842

Alfa AF: 0.864 Hom.: 26570

Bravo AF: 0.840

Asia WGS AF: 0.749 AC: 2605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.50
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs3769683; hg19: chr2-204578797;