2-203721314-C-G

Position:

• chr2-203721314-C-G

Variant summary

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

The NM_006139.4(CD28):​c.53-5319C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,158 control chromosomes in the GnomAD database, including 1,756 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 0.14 (1756 hom., cov: 32)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.836

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD28	NM_006139.4	c.53-5319C>G		intron_variant		ENST00000324106.9	NP_006130.1
CD28	NM_001410981.1	c.95-5319C>G		intron_variant			NP_001397910.1
CD28	NM_001243077.2	c.53-5319C>G		intron_variant			NP_001230006.1
CD28	NM_001243078.2	c.53-8334C>G		intron_variant			NP_001230007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD28	ENST00000324106.9	c.53-5319C>G		intron_variant		1	NM_006139.4	ENSP00000324890.7
CD28	ENST00000458610.6	c.95-5319C>G		intron_variant		1		ENSP00000393648.2
CD28	ENST00000374481.7	c.53-8334C>G		intron_variant		1		ENSP00000363605.4

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21918 AN: 152040 Hom.: 1755 Cov.: 32

Gnomad AFR AF: 0.0878

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0703

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.144 AC: 21928 AN: 152158 Hom.: 1756 Cov.: 32 AF XY: 0.141 AC XY: 10516 AN XY: 74414

Gnomad4 AFR AF: 0.0876

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.0704

Gnomad4 SAS AF: 0.0622

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.169

Alfa AF: 0.0701 Hom.: 94

Bravo AF: 0.147

Asia WGS AF: 0.0820 AC: 287 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	1.6
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: rs3116487; hg19: chr2-204586037;