2-203729003-G-A

Variant names:

• chr2-203729003-G-A
• rs3181107
• NM_006139.4:c.410-645G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006139.4(CD28):​c.410-645G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 152,214 control chromosomes in the GnomAD database, including 64,253 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 0.92 (64253 hom., cov: 31)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 6 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD28	NM_006139.4	MANE Select	c.410-645G>A		intron	N/A	NP_006130.1
	CD28	NM_001410981.1		c.452-645G>A		intron	N/A	NP_001397910.1
	CD28	NM_001243077.2		c.119-645G>A		intron	N/A	NP_001230006.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD28	ENST00000324106.9	TSL:1 MANE Select	c.410-645G>A		intron	N/A	ENSP00000324890.7
	CD28	ENST00000458610.6	TSL:1	c.452-645G>A		intron	N/A	ENSP00000393648.2
	CD28	ENST00000374481.8	TSL:1	c.53-645G>A		intron	N/A	ENSP00000363605.4

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139678 AN: 152096 Hom.: 64196 Cov.: 31

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.917

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

GnomAD4 genome AF: 0.918 AC: 139793 AN: 152214 Hom.: 64253 Cov.: 31 AF XY: 0.921 AC XY: 68543 AN XY: 74424

African (AFR) AF: 0.899 AC: 37349 AN: 41528

American (AMR) AF: 0.913 AC: 13962 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 3272 AN: 3470

East Asian (EAS) AF: 0.992 AC: 5116 AN: 5158

South Asian (SAS) AF: 0.971 AC: 4675 AN: 4816

European-Finnish (FIN) AF: 0.944 AC: 10010 AN: 10604

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.918 AC: 62425 AN: 68026

Other (OTH) AF: 0.916 AC: 1935 AN: 2112

Alfa AF: 0.923 Hom.: 23606

Bravo AF: 0.915

Asia WGS AF: 0.965 AC: 3347 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.48
PhyloP100		0.011
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: rs3181107; hg19: chr2-204593726;