rs35290181

chr2-203726762-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006139.4(CD28):c.182G>A(p.Ser61Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000514 in 1,614,022 control chromosomes in the GnomAD database, including 2 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 0.00022 (2 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: CD28 NM_006139.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.55

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01094991).
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD28	NM_006139.4	c.182G>A	p.Ser61Asn	missense_variant	2/4	ENST00000324106.9
CD28	NM_001410981.1	c.224G>A	p.Ser75Asn	missense_variant	2/4
CD28	NM_001243077.2	c.118+64G>A		intron_variant
CD28	NM_001243078.2	c.53-2886G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD28	ENST00000324106.9	c.182G>A	p.Ser61Asn	missense_variant	2/4	1	NM_006139.4	P1
CD28	ENST00000458610.6	c.224G>A	p.Ser75Asn	missense_variant	2/4	1
CD28	ENST00000374481.7	c.53-2886G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152158 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000358 AC: 9 AN: 251460 Hom.: 0 AF XY: 0.0000368 AC XY: 5 AN XY: 135900

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000791

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000342 AC: 50 AN: 1461864 Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000441

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152158 Hom.: 2 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74322

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000190 Hom.: 0

Bravo AF: 0.000283

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	23
Dann	Uncertain	0.99
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.011	T;T
MetaSVM	Benign	-0.84	T
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.46	N;N
REVEL	Benign	0.20
Sift	Benign	0.066	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.97	.;D
Vest4		0.29
MVP		0.72
MPC		0.55
ClinPred		0.50	T
GERP RS		4.8
Varity_R		0.13
gMVP		0.71

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: rs35290181; hg19: chr2-204591485;