2-203707954-G-T

Variant names:

• chr2-203707954-G-T
• rs1181390
• NM_006139.4:c.52+1206G>T

Variant summary

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

The ENST00000324106.9(CD28):​c.52+1206G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,066 control chromosomes in the GnomAD database, including 4,174 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 0.23 (4174 hom., cov: 32)
• Consequence: CD28 ENST00000324106.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000324106.9. 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.52+1206G>T		intron	N/A	NP_006130.1
	CD28	NM_001410981.1		c.94+1337G>T		intron	N/A	NP_001397910.1
	CD28	NM_001243077.2		c.52+1206G>T		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.52+1206G>T		intron	N/A	ENSP00000324890.7
	CD28	ENST00000458610.6	TSL:1	c.94+1337G>T		intron	N/A	ENSP00000393648.2
	CD28	ENST00000374481.8	TSL:1	c.52+1206G>T		intron	N/A	ENSP00000363605.4

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34230 AN: 151948 Hom.: 4162 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.226 AC: 34294 AN: 152066 Hom.: 4174 Cov.: 32 AF XY: 0.223 AC XY: 16575 AN XY: 74340

African (AFR) AF: 0.263 AC: 10909 AN: 41468

American (AMR) AF: 0.214 AC: 3263 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1024 AN: 3468

East Asian (EAS) AF: 0.445 AC: 2298 AN: 5164

South Asian (SAS) AF: 0.107 AC: 516 AN: 4830

European-Finnish (FIN) AF: 0.162 AC: 1707 AN: 10562

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13719 AN: 67984

Other (OTH) AF: 0.244 AC: 515 AN: 2112

Alfa AF: 0.178 Hom.: 1299

Bravo AF: 0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.3
DANN	Benign	0.65
PhyloP100		1.6
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: rs1181390; hg19: chr2-204572677; COSMIC: COSV107403406;