Variant rs35290181 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006139.4(CD28):c.182G>A(p.Ser61Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000514 in 1,614,022 control chromosomes in the GnomAD database, including 2 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 0.00022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CD28
NM_006139.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.55

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01094991).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD28	NM_006139.4 link	c.182G>A	p.Ser61Asn	missense_variant	2/4	ENST00000324106.9	NP_006130.1	P10747-1
CD28	NM_001410981.1 link	c.224G>A	p.Ser75Asn	missense_variant	2/4		NP_001397910.1
CD28	NM_001243077.2 link	c.118+64G>A		intron_variant			NP_001230006.1	P10747-4B4E0L1
CD28	NM_001243078.2 link	c.53-2886G>A		intron_variant			NP_001230007.1	P10747-2B4E0L1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD28	ENST00000324106.9 link	c.182G>A	p.Ser61Asn	missense_variant	2/4	1	NM_006139.4	ENSP00000324890.7	P10747-1
CD28	ENST00000458610.6 link	c.224G>A	p.Ser75Asn	missense_variant	2/4	1		ENSP00000393648.2	P10747-7
CD28	ENST00000374481.7 link	c.53-2886G>A		intron_variant		1		ENSP00000363605.4	P10747-2

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251460

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000342

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000441

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000217

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000190

Hom.:

Bravo

AF:

0.000283

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.43

.;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.2

.;M

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.46

N;N

REVEL

Benign

0.20

Sift

Benign

0.066

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.97

.;D

Vest4

0.29

MVP

0.72

MPC

0.55

ClinPred

0.50

GERP RS

4.8

Varity_R

0.13

gMVP

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over