chr2-203731534-A-G

Variant names:

• chr2-203731534-A-G
• rs3769686
• NM_006139.4:c.534+1762A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.56).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD28	NM_006139.4	c.534+1762A>G		intron_variant	Intron 3 of 3	ENST00000324106.9	NP_006130.1
CD28	NM_001410981.1	c.576+1762A>G		intron_variant	Intron 3 of 3		NP_001397910.1
CD28	NM_001243077.2	c.243+1762A>G		intron_variant	Intron 3 of 3		NP_001230006.1
CD28	NM_001243078.2	c.177+1762A>G		intron_variant	Intron 2 of 2		NP_001230007.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD28	ENST00000324106.9	c.534+1762A>G		intron_variant	Intron 3 of 3	1	NM_006139.4	ENSP00000324890.7
CD28	ENST00000458610.6	c.576+1762A>G		intron_variant	Intron 3 of 3	1		ENSP00000393648.2
CD28	ENST00000374481.8	c.177+1762A>G		intron_variant	Intron 2 of 2	1		ENSP00000363605.4
CD28	ENST00000718458.1	c.219+1762A>G		intron_variant	Intron 2 of 2			ENSP00000520836.1

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

African (AFR) AF: 0.00264 AC: 110 AN: 41588

American (AMR) AF: 0.00856 AC: 131 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3468

East Asian (EAS) AF: 0.0405 AC: 210 AN: 5182

South Asian (SAS) AF: 0.0133 AC: 64 AN: 4822

European-Finnish (FIN) AF: 0.0193 AC: 205 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00956 AC: 650 AN: 68020

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

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
PhyloP100		3.6
Mutation Taster		=100/0	polymorphism

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: rs3769686; hg19: chr2-204596257;