2-203729789-T-C

Position:

• chr2-203729789-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006139.4(CD28):​c.534+17T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,607,574 control chromosomes in the GnomAD database, including 22,979 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1696 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21283 hom.)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.91

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 2-203729789-T-C is Benign according to our data. Variant chr2-203729789-T-C is described in ClinVar as [Benign]. Clinvar id is 2688238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD28	NM_006139.4	c.534+17T>C		intron_variant		ENST00000324106.9
CD28	NM_001243077.2	c.243+17T>C		intron_variant
CD28	NM_001243078.2	c.177+17T>C		intron_variant
CD28	NM_001410981.1	c.576+17T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD28	ENST00000324106.9	c.534+17T>C		intron_variant		1	NM_006139.4	P1
CD28	ENST00000374481.7	c.177+17T>C		intron_variant		1
CD28	ENST00000458610.6	c.576+17T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20857 AN: 152086 Hom.: 1690 Cov.: 32

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.0749

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.161

GnomAD3 exomes AF: 0.147 AC: 35989 AN: 244856 Hom.: 2960 AF XY: 0.148 AC XY: 19596 AN XY: 132202

Gnomad AFR exome AF: 0.0520

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.266

Gnomad EAS exome AF: 0.101

Gnomad SAS exome AF: 0.0871

Gnomad FIN exome AF: 0.143

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.168

GnomAD4 exome AF: 0.165 AC: 240455 AN: 1455372 Hom.: 21283 Cov.: 31 AF XY: 0.164 AC XY: 118819 AN XY: 723782

Gnomad4 AFR exome AF: 0.0514

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.265

Gnomad4 EAS exome AF: 0.0823

Gnomad4 SAS exome AF: 0.0898

Gnomad4 FIN exome AF: 0.139

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.161

GnomAD4 genome AF: 0.137 AC: 20870 AN: 152202 Hom.: 1696 Cov.: 32 AF XY: 0.134 AC XY: 9932 AN XY: 74396

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.0965

Gnomad4 SAS AF: 0.0750

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.166

Alfa AF: 0.182 Hom.: 3712

Bravo AF: 0.135

Asia WGS AF: 0.0960 AC: 337 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 32% of patients studied by a panel of primary immunodeficiencies. Number of patients: 30. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.4
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3116496; hg19: chr2-204594512; COSMIC: COSV60730736;