rs2532502

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001242.5(CD27):c.698A>G(p.His233Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,614,090 control chromosomes in the GnomAD database, including 792,098 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H233L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.99 ( 75172 hom., cov: 31)

Exomes 𝑓: 0.99 ( 716926 hom. )

Consequence

CD27
NM_001242.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.374

Publications

29 publications found

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:43896): (CD27 antisense RNA 1)

CD27-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.73214E-7).

BP6

Variant 12-6451307-A-G is Benign according to our data. Variant chr12-6451307-A-G is described in ClinVar as Benign. ClinVar VariationId is 402517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD27	NM_001242.5	MANE Select	c.698A>G	p.His233Arg	missense	Exon 6 of 6	NP_001233.2	P26842
CD27	NM_001413263.1		c.791A>G	p.His264Arg	missense	Exon 7 of 7	NP_001400192.1
CD27	NM_001413264.1		c.671A>G	p.His224Arg	missense	Exon 6 of 6	NP_001400193.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CD27	ENST00000266557.4	TSL:1 MANE Select	c.698A>G	p.His233Arg	missense	Exon 6 of 6	ENSP00000266557.3	P26842
CD27-AS1	ENST00000399492.6	TSL:1	n.34+162T>C		intron	N/A
CD27-AS1	ENST00000504270.4	TSL:1	n.152+162T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.994

AC:

151187

AN:

152162

Hom.:

75112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.998

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.996

Gnomad ASJ

AF:

0.988

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.995

Gnomad FIN

AF:

0.998

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.989

Gnomad OTH

AF:

0.993

GnomAD2 exomes

AF:

0.993

AC:

249087

AN:

250914

AF XY:

0.992

show subpopulations

Gnomad AFR exome

AF:

0.998

Gnomad AMR exome

AF:

0.997

Gnomad ASJ exome

AF:

0.986

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.999

Gnomad NFE exome

AF:

0.989

Gnomad OTH exome

AF:

0.991

GnomAD4 exome

AF:

0.990

AC:

1447750

AN:

1461810

Hom.:

716926

Cov.:

AF XY:

0.990

AC XY:

720213

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.998

AC:

33426

AN:

33480

American (AMR)

AF:

0.997

AC:

44579

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.986

AC:

25773

AN:

26134

East Asian (EAS)

AF:

1.00

AC:

39699

AN:

39700

South Asian (SAS)

AF:

0.994

AC:

85725

AN:

86258

European-Finnish (FIN)

AF:

0.999

AC:

53312

AN:

53386

Middle Eastern (MID)

AF:

0.990

AC:

5712

AN:

5768

European-Non Finnish (NFE)

AF:

0.989

AC:

1099597

AN:

1111972

Other (OTH)

AF:

0.992

AC:

59927

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

696

1392

2089

2785

3481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21670

43340

65010

86680

108350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.994

AC:

151306

AN:

152280

Hom.:

75172

Cov.:

AF XY:

0.994

AC XY:

74012

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.998

AC:

41470

AN:

41546

American (AMR)

AF:

0.996

AC:

15237

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.988

AC:

3430

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5174

AN:

5174

South Asian (SAS)

AF:

0.995

AC:

4793

AN:

4818

European-Finnish (FIN)

AF:

0.998

AC:

10603

AN:

10622

Middle Eastern (MID)

AF:

0.990

AC:

291

AN:

294

European-Non Finnish (NFE)

AF:

0.989

AC:

67298

AN:

68034

Other (OTH)

AF:

0.993

AC:

2098

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

106

158

211

264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.990

Hom.:

143506

Bravo

AF:

0.993

TwinsUK

AF:

0.989

AC:

3666

ALSPAC

AF:

0.990

AC:

3815

ESP6500AA

AF:

0.996

AC:

4390

ESP6500EA

AF:

0.989

AC:

8508

ExAC

AF:

0.993

AC:

120514

Asia WGS

AF:

0.998

AC:

3469

AN:

3476

EpiCase

AF:

0.988

EpiControl

AF:

0.989

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Lymphoproliferative syndrome 2 (2)

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.21

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.12

MetaRNN

Benign

6.7e-7

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

0.37

PrimateAI

Benign

0.26

PROVEAN

Benign

0.15

REVEL

Benign

0.25

Sift

Benign

0.17

Sift4G

Uncertain

0.027

Polyphen

0.0

Vest4

0.010

MPC

0.23

ClinPred

0.0064

GERP RS

1.9

Varity_R

0.050

gMVP

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over