chr2-203710167-T-C

Variant names:

• chr2-203710167-T-C
• rs1181389
• NM_006139.4:c.52+3419T>C

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+3419T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,234 control chromosomes in the GnomAD database, including 1,807 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 0.14 (1807 hom., cov: 32)
• Consequence: CD28 NM_006139.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 13 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 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+3419T>C		intron	N/A	NP_006130.1
	CD28	NM_001410981.1		c.94+3550T>C		intron	N/A	NP_001397910.1
	CD28	NM_001243077.2		c.52+3419T>C		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+3419T>C		intron	N/A	ENSP00000324890.7
	CD28	ENST00000458610.6	TSL:1	c.94+3550T>C		intron	N/A	ENSP00000393648.2
	CD28	ENST00000374481.8	TSL:1	c.52+3419T>C		intron	N/A	ENSP00000363605.4

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21571 AN: 152116 Hom.: 1807 Cov.: 32

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0702

Gnomad SAS AF: 0.0585

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.142 AC: 21581 AN: 152234 Hom.: 1807 Cov.: 32 AF XY: 0.139 AC XY: 10333 AN XY: 74422

African (AFR) AF: 0.0566 AC: 2353 AN: 41560

American (AMR) AF: 0.171 AC: 2613 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3470

East Asian (EAS) AF: 0.0704 AC: 365 AN: 5184

South Asian (SAS) AF: 0.0585 AC: 282 AN: 4820

European-Finnish (FIN) AF: 0.148 AC: 1564 AN: 10588

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12739 AN: 68004

Other (OTH) AF: 0.175 AC: 371 AN: 2116

Alfa AF: 0.165 Hom.: 425

Bravo AF: 0.142

Asia WGS AF: 0.0800 AC: 280 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		-0.24
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: rs1181389; hg19: chr2-204574890;