rs10932017

Variant names:

• chr2-203713182-C-T
• rs10932017
• NM_006139.4:c.52+6434C>T

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+6434C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,034 control chromosomes in the GnomAD database, including 18,889 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 0.49 (18889 hom., cov: 33)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.267
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006139.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD28	NM_006139.4	MANE Select	c.52+6434C>T		intron	N/A	NP_006130.1
	CD28	NM_001410981.1		c.94+6565C>T		intron	N/A	NP_001397910.1
	CD28	NM_001243077.2		c.52+6434C>T		intron	N/A	NP_001230006.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD28	ENST00000324106.9	TSL:1 MANE Select	c.52+6434C>T		intron	N/A	ENSP00000324890.7
	CD28	ENST00000458610.6	TSL:1	c.94+6565C>T		intron	N/A	ENSP00000393648.2
	CD28	ENST00000374481.8	TSL:1	c.52+6434C>T		intron	N/A	ENSP00000363605.4

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75051 AN: 151916 Hom.: 18888 Cov.: 33

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.494 AC: 75077 AN: 152034 Hom.: 18889 Cov.: 33 AF XY: 0.492 AC XY: 36530 AN XY: 74310

African (AFR) AF: 0.416 AC: 17238 AN: 41438

American (AMR) AF: 0.498 AC: 7608 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2295 AN: 3466

East Asian (EAS) AF: 0.351 AC: 1816 AN: 5178

South Asian (SAS) AF: 0.663 AC: 3194 AN: 4820

European-Finnish (FIN) AF: 0.477 AC: 5036 AN: 10568

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36137 AN: 67974

Other (OTH) AF: 0.519 AC: 1097 AN: 2112

Alfa AF: 0.519 Hom.: 30699

Bravo AF: 0.489

Asia WGS AF: 0.533 AC: 1857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.74
DANN	Benign	0.39
PhyloP100		-0.27
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: rs10932017; hg19: chr2-204577905;