Genetic Variant CD28:c.534+17T>C (chr2-203729789-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.91

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	Exon rank	MANE	Protein	UniProt
CD28	NM_006139.4 link	c.534+17T>C	intron_variant	Intron 3 of 3	ENST00000324106.9	NP_006130.1	P10747-1
CD28	NM_001410981.1 link	c.576+17T>C	intron_variant	Intron 3 of 3		NP_001397910.1
CD28	NM_001243077.2 link	c.243+17T>C	intron_variant	Intron 3 of 3		NP_001230006.1	P10747-4B4E0L1
CD28	NM_001243078.2 link	c.177+17T>C	intron_variant	Intron 2 of 2		NP_001230007.1	P10747-2B4E0L1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CD28	ENST00000324106.9 link	c.534+17T>C	intron_variant	Intron 3 of 3	1	NM_006139.4	ENSP00000324890.7	P10747-1
CD28	ENST00000458610.6 link	c.576+17T>C	intron_variant	Intron 3 of 3	1		ENSP00000393648.2	P10747-7
CD28	ENST00000374481.7 link	c.177+17T>C	intron_variant	Intron 2 of 2	1		ENSP00000363605.4	P10747-2

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20857

AN:

152086

Hom.:

1690

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.164

AC XY:

118819

AN XY:

723782

show subpopulations

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.:

AF XY:

0.134

AC XY:

9932

AN XY:

74396

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over