rs25680

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001242.5(CD27):c.175G>A(p.Ala59Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,613,860 control chromosomes in the GnomAD database, including 41,005 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3005 hom., cov: 31)

Exomes 𝑓: 0.22 ( 38000 hom. )

Consequence

CD27
NM_001242.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.872

Variant links:

Genes affected

CD27 (HGNC:11922): (CD27 molecule) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is required for generation and long-term maintenance of T cell immunity. It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis. This receptor transduces signals that lead to the activation of NF-kappaB and MAPK8/JNK. Adaptor proteins TRAF2 and TRAF5 have been shown to mediate the signaling process of this receptor. CD27-binding protein (SIVA), a proapoptotic protein, can bind to this receptor and is thought to play an important role in the apoptosis induced by this receptor. [provided by RefSeq, Jul 2008]

CD27 links:

CD27-AS1 (HGNC:):

CD27-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044418573).

BP6

Variant 12-6445462-G-A is Benign according to our data. Variant chr12-6445462-G-A is described in ClinVar as [Benign]. Clinvar id is 1168241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD27	NM_001242.5 linkuse as main transcript	c.175G>A	p.Ala59Thr	missense_variant	2/6	ENST00000266557.4	NP_001233.2	P26842

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD27	ENST00000266557.4 linkuse as main transcript	c.175G>A	p.Ala59Thr	missense_variant	2/6	1	NM_001242.5	ENSP00000266557.3		P26842

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29458

AN:

152006

Hom.:

3008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.0568

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.179

GnomAD3 exomes

AF:

0.191

AC:

47909

AN:

251384

Hom.:

5234

AF XY:

0.200

AC XY:

27158

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.175

Gnomad AMR exome

AF:

0.0938

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.0590

Gnomad SAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.191

GnomAD4 exome

AF:

0.222

AC:

325207

AN:

1461736

Hom.:

38000

Cov.:

AF XY:

0.225

AC XY:

163421

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.167

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.0404

Gnomad4 SAS exome

AF:

0.286

Gnomad4 FIN exome

AF:

0.176

Gnomad4 NFE exome

AF:

0.235

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.194

AC:

29443

AN:

152124

Hom.:

3005

Cov.:

AF XY:

0.191

AC XY:

14180

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.144

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.0569

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.165

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.177

Alfa

AF:

0.214

Hom.:

9174

Bravo

AF:

0.186

TwinsUK

AF:

0.235

AC:

872

ALSPAC

AF:

0.255

AC:

981

ESP6500AA

AF:

0.176

AC:

777

ESP6500EA

AF:

0.230

AC:

1977

ExAC

AF:

0.198

AC:

24007

Asia WGS

AF:

0.173

AC:

604

AN:

3478

EpiCase

AF:

0.222

EpiControl

AF:

0.217

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 24. Only high quality variants are reported. -

Lymphoproliferative syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.28

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0044

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.75

REVEL

Benign

0.13

Sift

Benign

0.77

Sift4G

Benign

0.52

Polyphen

0.47

Vest4

0.11

MPC

0.52

ClinPred

0.018

GERP RS

2.7

Varity_R

0.083

gMVP

0.54

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over