chr2-203726685-G-A

Position:

• chr2-203726685-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006139.4(CD28):​c.105G>A​(p.Ala35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,613,932 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0074 (4 hom., cov: 32)
  • Exomes 𝑓: 0.012 (131 hom.)
• Consequence: CD28 NM_006139.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.24

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-203726685-G-A is Benign according to our data. Variant chr2-203726685-G-A is described in ClinVar as [Benign]. Clinvar id is 774413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD28	NM_006139.4	c.105G>A	p.Ala35=	synonymous_variant	2/4	ENST00000324106.9
CD28	NM_001410981.1	c.147G>A	p.Ala49=	synonymous_variant	2/4
CD28	NM_001243077.2	c.105G>A	p.Ala35=	synonymous_variant	2/4
CD28	NM_001243078.2	c.53-2963G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD28	ENST00000324106.9	c.105G>A	p.Ala35=	synonymous_variant	2/4	1	NM_006139.4	P1
CD28	ENST00000458610.6	c.147G>A	p.Ala49=	synonymous_variant	2/4	1
CD28	ENST00000374481.7	c.53-2963G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00740 AC: 1124 AN: 151984 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00603

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.00908

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0119

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00712 AC: 1791 AN: 251418 Hom.: 19 AF XY: 0.00701 AC XY: 952 AN XY: 135886

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00393

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000621

Gnomad FIN exome AF: 0.0105

Gnomad NFE exome AF: 0.0115

Gnomad OTH exome AF: 0.00799

GnomAD4 exome AF: 0.0117 AC: 17136 AN: 1461830 Hom.: 131 Cov.: 32 AF XY: 0.0112 AC XY: 8175 AN XY: 727222

Gnomad4 AFR exome AF: 0.00167

Gnomad4 AMR exome AF: 0.00389

Gnomad4 ASJ exome AF: 0.00226

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000510

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.0139

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.00739 AC: 1124 AN: 152102 Hom.: 4 Cov.: 32 AF XY: 0.00751 AC XY: 558 AN XY: 74346

Gnomad4 AFR AF: 0.00239

Gnomad4 AMR AF: 0.00602

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000625

Gnomad4 FIN AF: 0.00908

Gnomad4 NFE AF: 0.0119

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00996 Hom.: 6

Bravo AF: 0.00722

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0115

EpiControl AF: 0.00960

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.38

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: rs41272649; hg19: chr2-204591408;