2-203720779-T-C

Position:

• chr2-203720779-T-C

Variant summary

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

The NM_006139.4(CD28):​c.53-5854T>C 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 152,252 control chromosomes in the GnomAD database, including 1,765 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 (1765 hom., cov: 32)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770

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=-0.66).
• 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.53-5854T>C		intron_variant		ENST00000324106.9	NP_006130.1
CD28	NM_001243077.2	c.53-5854T>C		intron_variant			NP_001230006.1
CD28	NM_001243078.2	c.53-8869T>C		intron_variant			NP_001230007.1
CD28	NM_001410981.1	c.95-5854T>C		intron_variant			NP_001397910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD28	ENST00000324106.9	c.53-5854T>C		intron_variant		1	NM_006139.4	ENSP00000324890	P1
CD28	ENST00000374481.7	c.53-8869T>C		intron_variant		1		ENSP00000363605
CD28	ENST00000458610.6	c.95-5854T>C		intron_variant		1		ENSP00000393648

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21950 AN: 152134 Hom.: 1764 Cov.: 32

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.304

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0709

Gnomad SAS AF: 0.0624

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.178

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: 21960 AN: 152252 Hom.: 1765 Cov.: 32 AF XY: 0.141 AC XY: 10523 AN XY: 74428

Gnomad4 AFR AF: 0.0878

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.0711

Gnomad4 SAS AF: 0.0624

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.169

Alfa AF: 0.156 Hom.: 246

Bravo AF: 0.147

Asia WGS AF: 0.0810 AC: 286 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.7
DANN	Benign	0.90

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: rs3116486; hg19: chr2-204585502;