rs3769686

Positions:

• chr2-203731534-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006139.4(CD28):​c.534+1762A>G variant causes a intron change. The variant allele was found at a frequency of 0.00955 in 152,320 control chromosomes in the GnomAD database, including 11 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 0.0096 (11 hom., cov: 32)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.59

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=-0.56).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00955 (1455/152320) while in subpopulation EAS AF= 0.0405 (210/5182). AF 95% confidence interval is 0.036. There are 11 homozygotes in gnomad4. There are 758 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD28	NM_006139.4	c.534+1762A>G		intron_variant		ENST00000324106.9	NP_006130.1
CD28	NM_001243077.2	c.243+1762A>G		intron_variant			NP_001230006.1
CD28	NM_001243078.2	c.177+1762A>G		intron_variant			NP_001230007.1
CD28	NM_001410981.1	c.576+1762A>G		intron_variant			NP_001397910.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD28	ENST00000324106.9	c.534+1762A>G		intron_variant		1	NM_006139.4	ENSP00000324890	P1
CD28	ENST00000374481.7	c.177+1762A>G		intron_variant		1		ENSP00000363605
CD28	ENST00000458610.6	c.576+1762A>G		intron_variant		1		ENSP00000393648

Frequencies

GnomAD3 genomes AF: 0.00953 AC: 1450 AN: 152202 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.0404

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00955

Gnomad OTH AF: 0.0110

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

GnomAD4 genome AF: 0.00955 AC: 1455 AN: 152320 Hom.: 11 Cov.: 32 AF XY: 0.0102 AC XY: 758 AN XY: 74482

Gnomad4 AFR AF: 0.00264

Gnomad4 AMR AF: 0.00856

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.0405

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.0193

Gnomad4 NFE AF: 0.00956

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00817 Hom.: 1

Bravo AF: 0.00886

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Benign	0.80

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: rs3769686; hg19: chr2-204596257;