2-203714074-A-G

Variant names:

• chr2-203714074-A-G
• rs3769683
• NM_006139.4:c.52+7326A>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+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
• Publications: 11 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: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CD28	NM_006139.4	c.52+7326A>G		intron_variant	Intron 1 of 3	ENST00000324106.9	NP_006130.1
CD28	NM_001410981.1	c.94+7457A>G		intron_variant	Intron 1 of 3		NP_001397910.1
CD28	NM_001243077.2	c.52+7326A>G		intron_variant	Intron 1 of 3		NP_001230006.1
CD28	NM_001243078.2	c.52+7326A>G		intron_variant	Intron 1 of 2		NP_001230007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD28	ENST00000324106.9	c.52+7326A>G		intron_variant	Intron 1 of 3	1	NM_006139.4	ENSP00000324890.7
CD28	ENST00000458610.6	c.94+7457A>G		intron_variant	Intron 1 of 3	1		ENSP00000393648.2
CD28	ENST00000374481.8	c.52+7326A>G		intron_variant	Intron 1 of 2	1		ENSP00000363605.4
CD28	ENST00000718458.1	c.94+7457A>G		intron_variant	Intron 1 of 2			ENSP00000520836.1

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

African (AFR) AF: 0.857 AC: 35533 AN: 41446

American (AMR) AF: 0.815 AC: 12446 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.906 AC: 3145 AN: 3472

East Asian (EAS) AF: 0.520 AC: 2691 AN: 5174

South Asian (SAS) AF: 0.897 AC: 4305 AN: 4800

European-Finnish (FIN) AF: 0.883 AC: 9330 AN: 10572

Middle Eastern (MID) AF: 0.860 AC: 251 AN: 292

European-Non Finnish (NFE) AF: 0.866 AC: 58843 AN: 67960

Other (OTH) AF: 0.842 AC: 1781 AN: 2116

Alfa AF: 0.865 Hom.: 29490

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
PhyloP100		0.012
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: rs3769683; hg19: chr2-204578797;