NM_006139.4:c.53-698A>T

Variant names:

• chr2-203725935-A-T
• rs2013278
• NM_006139.4:c.53-698A>T

Variant summary

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

The NM_006139.4(CD28):​c.53-698A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,112 control chromosomes in the GnomAD database, including 32,034 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 0.64 (32034 hom., cov: 33)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.21
• Publications: 4 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=-1.14).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD28	NM_006139.4	c.53-698A>T		intron_variant	Intron 1 of 3	ENST00000324106.9	NP_006130.1
CD28	NM_001410981.1	c.95-698A>T		intron_variant	Intron 1 of 3		NP_001397910.1
CD28	NM_001243077.2	c.53-698A>T		intron_variant	Intron 1 of 3		NP_001230006.1
CD28	NM_001243078.2	c.53-3713A>T		intron_variant	Intron 1 of 2		NP_001230007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD28	ENST00000324106.9	c.53-698A>T		intron_variant	Intron 1 of 3	1	NM_006139.4	ENSP00000324890.7
CD28	ENST00000458610.6	c.95-698A>T		intron_variant	Intron 1 of 3	1		ENSP00000393648.2
CD28	ENST00000374481.8	c.53-3713A>T		intron_variant	Intron 1 of 2	1		ENSP00000363605.4
CD28	ENST00000718458.1	c.95-3713A>T		intron_variant	Intron 1 of 2			ENSP00000520836.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97913 AN: 151994 Hom.: 32030 Cov.: 33

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.644 AC: 97948 AN: 152112 Hom.: 32034 Cov.: 33 AF XY: 0.646 AC XY: 48051 AN XY: 74366

African (AFR) AF: 0.570 AC: 23621 AN: 41472

American (AMR) AF: 0.620 AC: 9481 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2233 AN: 3472

East Asian (EAS) AF: 0.406 AC: 2097 AN: 5164

South Asian (SAS) AF: 0.819 AC: 3953 AN: 4824

European-Finnish (FIN) AF: 0.738 AC: 7816 AN: 10586

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46759 AN: 67976

Other (OTH) AF: 0.629 AC: 1330 AN: 2114

Alfa AF: 0.662 Hom.: 3521

Bravo AF: 0.625

Asia WGS AF: 0.632 AC: 2195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.046
DANN	Benign	0.055
PhyloP100		-5.2
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: rs2013278; hg19: chr2-204590658;