dbSNP rs2267966: CD27:c.269-2147A>T (chr12-6448026-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001242.5(CD27):c.269-2147A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,136 control chromosomes in the GnomAD database, including 4,625 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 0.22 ( 4621 hom., cov: 31)

Exomes 𝑓: 0.21 ( 4 hom. )

Consequence

CD27
NM_001242.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.146

Publications

11 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

new If you want to explore the variant's impact on the transcript NM_001242.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 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.269-2147A>T	intron	N/A	NP_001233.2	P26842
CD27	NM_001413263.1		c.361+1794A>T	intron	N/A	NP_001400192.1
CD27	NM_001413264.1		c.242-2147A>T	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.269-2147A>T	intron	N/A	ENSP00000266557.3	P26842
CD27-AS1	ENST00000504270.4	TSL:1	n.395T>A	non_coding_transcript_exon	Exon 3 of 3
CD27-AS1	ENST00000537003.2	TSL:1	n.914T>A	non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33808

AN:

151864

Hom.:

4619

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0545

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.357

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.249

GnomAD4 exome

AF:

0.214

AC:

AN:

154

Hom.:

Cov.:

AF XY:

0.230

AC XY:

AN XY:

100

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.283

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.202

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.223

AC:

33826

AN:

151982

Hom.:

4621

Cov.:

AF XY:

0.223

AC XY:

16589

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.0544

AC:

2256

AN:

41488

American (AMR)

AF:

0.285

AC:

4354

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1084

AN:

3468

East Asian (EAS)

AF:

0.357

AC:

1841

AN:

5162

South Asian (SAS)

AF:

0.182

AC:

879

AN:

4818

European-Finnish (FIN)

AF:

0.308

AC:

3247

AN:

10536

Middle Eastern (MID)

AF:

0.262

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.282

AC:

19189

AN:

67950

Other (OTH)

AF:

0.249

AC:

524

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1244

2487

3731

4974

6218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.241

Hom.:

625

Bravo

AF:

0.220

Asia WGS

AF:

0.229

AC:

793

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.5

(source)

DANN

Benign

0.64

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over