chr2-203707311-C-G

Variant names:

• chr2-203707311-C-G
• rs3181101
• NM_006139.4:c.52+563C>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+563C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 152,088 control chromosomes in the GnomAD database, including 742 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 0.087 (742 hom., cov: 31)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD28	NM_006139.4	MANE Select	c.52+563C>G		intron	N/A	NP_006130.1	P10747-1
	CD28	NM_001410981.1		c.94+694C>G		intron	N/A	NP_001397910.1	P10747-7
	CD28	NM_001243077.2		c.52+563C>G		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.52+563C>G		intron	N/A	ENSP00000324890.7	P10747-1
	CD28	ENST00000458610.6	TSL:1	c.94+694C>G		intron	N/A	ENSP00000393648.2	P10747-7
	CD28	ENST00000374481.8	TSL:1	c.52+563C>G		intron	N/A	ENSP00000363605.4	P10747-2

Frequencies

GnomAD3 genomes AF: 0.0867 AC: 13175 AN: 151970 Hom.: 742 Cov.: 31

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0770

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0943

Gnomad FIN AF: 0.0775

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.0989

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

GnomAD4 genome AF: 0.0866 AC: 13170 AN: 152088 Hom.: 742 Cov.: 31 AF XY: 0.0828 AC XY: 6157 AN XY: 74340

African (AFR) AF: 0.0249 AC: 1035 AN: 41484

American (AMR) AF: 0.0768 AC: 1173 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 387 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5180

South Asian (SAS) AF: 0.0950 AC: 458 AN: 4820

European-Finnish (FIN) AF: 0.0775 AC: 818 AN: 10552

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.132 AC: 8974 AN: 67986

Other (OTH) AF: 0.0970 AC: 205 AN: 2114

Alfa AF: 0.0567 Hom.: 61

Bravo AF: 0.0841

Asia WGS AF: 0.0430 AC: 151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.96
DANN	Benign	0.71
PhyloP100		-1.1
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: rs3181101; hg19: chr2-204572034;