chr2-203707954-G-T

Position:

• chr2-203707954-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006139.4(CD28):​c.52+1206G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,066 control chromosomes in the GnomAD database, including 4,174 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 0.23 (4174 hom., cov: 32)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD28	NM_006139.4	c.52+1206G>T		intron_variant		ENST00000324106.9	NP_006130.1
CD28	NM_001410981.1	c.94+1337G>T		intron_variant			NP_001397910.1
CD28	NM_001243077.2	c.52+1206G>T		intron_variant			NP_001230006.1
CD28	NM_001243078.2	c.52+1206G>T		intron_variant			NP_001230007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD28	ENST00000324106.9	c.52+1206G>T		intron_variant		1	NM_006139.4	ENSP00000324890.7
CD28	ENST00000458610.6	c.94+1337G>T		intron_variant		1		ENSP00000393648.2
CD28	ENST00000374481.7	c.52+1206G>T		intron_variant		1		ENSP00000363605.4

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34230 AN: 151948 Hom.: 4162 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.226 AC: 34294 AN: 152066 Hom.: 4174 Cov.: 32 AF XY: 0.223 AC XY: 16575 AN XY: 74340

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.244

Alfa AF: 0.174 Hom.: 1126

Bravo AF: 0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.3
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs1181390; hg19: chr2-204572677;