Genetic Variant CD27:c.269-9T>C (chr12-6450164-T-C) – ACMG Classification: Benign (-20 pts)

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.269-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,609,108 control chromosomes in the GnomAD database, including 259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 144 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 115 hom. )

Consequence

CD27
NM_001242.5 intron

Scores

Splicing: ADA: 0.0001778

Clinical Significance

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

Conservation

PhyloP100: -0.0250

Publications

1 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 (BayesDel_noAF=-0.73).

BP6

Variant 12-6450164-T-C is Benign according to our data. Variant chr12-6450164-T-C is described in ClinVar as Benign. ClinVar VariationId is 473871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0777 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	Effect	Exon Rank	Protein	UniProt
CD27	NM_001242.5	MANE Select	c.269-9T>C	intron	N/A	NP_001233.2	P26842
CD27	NM_001413263.1		c.362-9T>C	intron	N/A	NP_001400192.1
CD27	NM_001413264.1		c.242-9T>C	intron	N/A	NP_001400193.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CD27	ENST00000266557.4	TSL:1 MANE Select	c.269-9T>C	intron	N/A	ENSP00000266557.3	P26842
CD27-AS1	ENST00000399492.6	TSL:1	n.145+706A>G	intron	N/A
CD27-AS1	ENST00000504270.4	TSL:1	n.152+1305A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0232

AC:

3526

AN:

152108

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0801

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00811

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.00652

AC:

1613

AN:

247298

AF XY:

0.00485

show subpopulations

Gnomad AFR exome

AF:

0.0795

Gnomad AMR exome

AF:

0.00478

Gnomad ASJ exome

AF:

0.00735

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000586

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00265

AC:

3861

AN:

1456882

Hom.:

115

Cov.:

AF XY:

0.00239

AC XY:

1730

AN XY:

724926

show subpopulations

African (AFR)

AF:

0.0814

AC:

2723

AN:

33466

American (AMR)

AF:

0.00544

AC:

243

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.00704

AC:

183

AN:

26012

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000929

AC:

AN:

86098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49752

Middle Eastern (MID)

AF:

0.00486

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000325

AC:

361

AN:

1111120

Other (OTH)

AF:

0.00522

AC:

315

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

186

371

557

742

928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.0232

AC:

3532

AN:

152226

Hom.:

144

Cov.:

AF XY:

0.0224

AC XY:

1667

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0800

AC:

3320

AN:

41498

American (AMR)

AF:

0.00804

AC:

123

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000632

AC:

AN:

68018

Other (OTH)

AF:

0.0118

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

159

318

476

635

794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0127

Hom.:

Bravo

AF:

0.0263

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.000712

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Lymphoproliferative syndrome 2 (2)

Autoinflammatory syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.9

(source)

DANN

Benign

0.81

PhyloP100

-0.025

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00018

dbscSNV1_RF

Benign

0.016

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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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