2-203707283-G-C

Variant names:

• chr2-203707283-G-C
• rs3181100
• NM_006139.4:c.52+535G>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.52+535G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 151,806 control chromosomes in the GnomAD database, including 28,140 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 0.61 (28140 hom., cov: 31)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD28	NM_006139.4	c.52+535G>C		intron_variant	Intron 1 of 3	ENST00000324106.9	NP_006130.1
CD28	NM_001410981.1	c.94+666G>C		intron_variant	Intron 1 of 3		NP_001397910.1
CD28	NM_001243077.2	c.52+535G>C		intron_variant	Intron 1 of 3		NP_001230006.1
CD28	NM_001243078.2	c.52+535G>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.52+535G>C		intron_variant	Intron 1 of 3	1	NM_006139.4	ENSP00000324890.7
CD28	ENST00000458610.6	c.94+666G>C		intron_variant	Intron 1 of 3	1		ENSP00000393648.2
CD28	ENST00000374481.8	c.52+535G>C		intron_variant	Intron 1 of 2	1		ENSP00000363605.4
CD28	ENST00000718458.1	c.94+666G>C		intron_variant	Intron 1 of 2			ENSP00000520836.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91836 AN: 151688 Hom.: 28120 Cov.: 31

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.605 AC: 91907 AN: 151806 Hom.: 28140 Cov.: 31 AF XY: 0.607 AC XY: 45045 AN XY: 74176

African (AFR) AF: 0.595 AC: 24614 AN: 41344

American (AMR) AF: 0.617 AC: 9429 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2380 AN: 3468

East Asian (EAS) AF: 0.855 AC: 4429 AN: 5178

South Asian (SAS) AF: 0.771 AC: 3710 AN: 4814

European-Finnish (FIN) AF: 0.555 AC: 5811 AN: 10474

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39509 AN: 67946

Other (OTH) AF: 0.622 AC: 1310 AN: 2106

Alfa AF: 0.592 Hom.: 3307

Bravo AF: 0.609

Asia WGS AF: 0.784 AC: 2728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.65
DANN	Benign	0.61
PhyloP100		-1.0
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: rs3181100; hg19: chr2-204572006;