chr2-203721314-C-A

Variant names:

• chr2-203721314-C-A
• rs3116487
• NM_006139.4:c.53-5319C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006139.4(CD28):​c.53-5319C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000526 in 152,192 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000053 (0 hom., cov: 32)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.53-5319C>A		intron	N/A	NP_006130.1	P10747-1
	CD28	NM_001410981.1		c.95-5319C>A		intron	N/A	NP_001397910.1	P10747-7
	CD28	NM_001243077.2		c.53-5319C>A		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.53-5319C>A		intron	N/A	ENSP00000324890.7	P10747-1
	CD28	ENST00000458610.6	TSL:1	c.95-5319C>A		intron	N/A	ENSP00000393648.2	P10747-7
	CD28	ENST00000374481.8	TSL:1	c.53-8334C>A		intron	N/A	ENSP00000363605.4	P10747-2

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152074 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74426

African (AFR) AF: 0.00 AC: 0 AN: 41532

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 94

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.72
PhyloP100		-0.84

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: rs3116487; hg19: chr2-204586037;