rs3769683

Variant names:

• chr2-203714074-A-C
• rs3769683
• NM_006139.4:c.52+7326A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-203714074-A-C
• chr2-203714074-A-G
• chr2-203714074-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006139.4(CD28):​c.52+7326A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD28	NM_006139.4	c.52+7326A>C		intron_variant	Intron 1 of 3	ENST00000324106.9	NP_006130.1
CD28	NM_001410981.1	c.94+7457A>C		intron_variant	Intron 1 of 3		NP_001397910.1
CD28	NM_001243077.2	c.52+7326A>C		intron_variant	Intron 1 of 3		NP_001230006.1
CD28	NM_001243078.2	c.52+7326A>C		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>C		intron_variant	Intron 1 of 3	1	NM_006139.4	ENSP00000324890.7
CD28	ENST00000458610.6	c.94+7457A>C		intron_variant	Intron 1 of 3	1		ENSP00000393648.2
CD28	ENST00000374481.8	c.52+7326A>C		intron_variant	Intron 1 of 2	1		ENSP00000363605.4
CD28	ENST00000718458.1	c.94+7457A>C		intron_variant	Intron 1 of 2			ENSP00000520836.1

Frequencies

GnomAD3 genomes Cov.: 28

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

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.43
DANN	Benign	0.71
PhyloP100		0.012

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;