2-203717900-T-C

Variant names:

• chr2-203717900-T-C
• rs4673259
• NM_006139.4:c.53-8733T>C

Variant summary

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

The NM_006139.4(CD28):​c.53-8733T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0637 in 152,236 control chromosomes in the GnomAD database, including 804 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 0.064 (804 hom., cov: 32)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.344
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD28	NM_006139.4	c.53-8733T>C		intron_variant	Intron 1 of 3	ENST00000324106.9	NP_006130.1
CD28	NM_001410981.1	c.95-8733T>C		intron_variant	Intron 1 of 3		NP_001397910.1
CD28	NM_001243077.2	c.53-8733T>C		intron_variant	Intron 1 of 3		NP_001230006.1
CD28	NM_001243078.2	c.52+11152T>C		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.53-8733T>C		intron_variant	Intron 1 of 3	1	NM_006139.4	ENSP00000324890.7
CD28	ENST00000458610.6	c.95-8733T>C		intron_variant	Intron 1 of 3	1		ENSP00000393648.2
CD28	ENST00000374481.8	c.52+11152T>C		intron_variant	Intron 1 of 2	1		ENSP00000363605.4
CD28	ENST00000718458.1	c.94+11283T>C		intron_variant	Intron 1 of 2			ENSP00000520836.1

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9678 AN: 152118 Hom.: 807 Cov.: 32

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0948

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.0583

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0679

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

GnomAD4 genome AF: 0.0637 AC: 9692 AN: 152236 Hom.: 804 Cov.: 32 AF XY: 0.0679 AC XY: 5054 AN XY: 74432

African (AFR) AF: 0.0422 AC: 1754 AN: 41554

American (AMR) AF: 0.0952 AC: 1457 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2435 AN: 5164

South Asian (SAS) AF: 0.0699 AC: 337 AN: 4820

European-Finnish (FIN) AF: 0.0583 AC: 619 AN: 10612

Middle Eastern (MID) AF: 0.0308 AC: 9 AN: 292

European-Non Finnish (NFE) AF: 0.0416 AC: 2828 AN: 68002

Other (OTH) AF: 0.0663 AC: 140 AN: 2112

Alfa AF: 0.0534 Hom.: 813

Bravo AF: 0.0695

Asia WGS AF: 0.212 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.78
PhyloP100		-0.34
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: rs4673259; hg19: chr2-204582623;