2-203707417-A-T

Variant names:

• chr2-203707417-A-T
• rs2140148
• NM_006139.4:c.52+669A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006139.4(CD28):​c.52+669A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 152,234 control chromosomes in the GnomAD database, including 5 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 0.0045 (5 hom., cov: 32)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.392
• Publications: 11 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD28	NM_006139.4	c.52+669A>T		intron_variant	Intron 1 of 3	ENST00000324106.9	NP_006130.1
CD28	NM_001410981.1	c.94+800A>T		intron_variant	Intron 1 of 3		NP_001397910.1
CD28	NM_001243077.2	c.52+669A>T		intron_variant	Intron 1 of 3		NP_001230006.1
CD28	NM_001243078.2	c.52+669A>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.52+669A>T		intron_variant	Intron 1 of 3	1	NM_006139.4	ENSP00000324890.7
CD28	ENST00000458610.6	c.94+800A>T		intron_variant	Intron 1 of 3	1		ENSP00000393648.2
CD28	ENST00000374481.8	c.52+669A>T		intron_variant	Intron 1 of 2	1		ENSP00000363605.4
CD28	ENST00000718458.1	c.94+800A>T		intron_variant	Intron 1 of 2			ENSP00000520836.1

Frequencies

GnomAD3 genomes AF: 0.00448 AC: 681 AN: 152114 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00287

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

GnomAD4 genome AF: 0.00448 AC: 682 AN: 152234 Hom.: 5 Cov.: 32 AF XY: 0.00411 AC XY: 306 AN XY: 74410

African (AFR) AF: 0.0155 AC: 645 AN: 41556

American (AMR) AF: 0.00183 AC: 28 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.00284 AC: 6 AN: 2112

Alfa AF: 0.00 Hom.: 2766

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.22
DANN	Benign	0.74
PhyloP100		-0.39

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: rs2140148; hg19: chr2-204572140;