rs3181107

Positions:

• chr2-203729003-G-A
• chr2-203729003-G-C
• chr2-203729003-G-T

Variant summary

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

The NM_006139.4(CD28):​c.410-645G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 152,214 control chromosomes in the GnomAD database, including 64,253 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 0.92 (64253 hom., cov: 31)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD28	NM_006139.4	c.410-645G>A		intron_variant		ENST00000324106.9
CD28	NM_001243077.2	c.119-645G>A		intron_variant
CD28	NM_001243078.2	c.53-645G>A		intron_variant
CD28	NM_001410981.1	c.452-645G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD28	ENST00000324106.9	c.410-645G>A		intron_variant		1	NM_006139.4	P1
CD28	ENST00000374481.7	c.53-645G>A		intron_variant		1
CD28	ENST00000458610.6	c.452-645G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139678 AN: 152096 Hom.: 64196 Cov.: 31

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.918

Gnomad OTH AF: 0.917

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

GnomAD4 genome AF: 0.918 AC: 139793 AN: 152214 Hom.: 64253 Cov.: 31 AF XY: 0.921 AC XY: 68543 AN XY: 74424

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.913

Gnomad4 ASJ AF: 0.943

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.971

Gnomad4 FIN AF: 0.944

Gnomad4 NFE AF: 0.918

Gnomad4 OTH AF: 0.916

Alfa AF: 0.921 Hom.: 12913

Bravo AF: 0.915

Asia WGS AF: 0.965 AC: 3347 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.48

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: rs3181107; hg19: chr2-204593726;