Genetic Variant ENST00000399492.6:n.485-948_485-947insC (chr12-6444664-T-TG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000399492.6(CD27-AS1):n.485-948_485-947insC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.28 ( 1866 hom., cov: 0)

Consequence

CD27-AS1
ENST00000399492.6 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.06

Publications

0 publications found

Variant links:

COSMIC-nc: COSV56949552

Genes affected

CD27-AS1 (HGNC:43896): (CD27 antisense RNA 1)

CD27-AS1 links:

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 Gene-Disease associations (from GenCC):

lymphoproliferative syndrome 2
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
autosomal recessive lymphoproliferative disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CD27 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 12-6444664-T-TG is Benign according to our data. Variant chr12-6444664-T-TG is described in ClinVar as [Benign]. Clinvar id is 1260079.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
CD27	NM_001413266.1 link	c.-315+554dupG	intron_variant	Intron 1 of 5	NP_001400195.1
CD27	NM_001413267.1 link	c.-403+554dupG	intron_variant	Intron 1 of 6	NP_001400196.1
CD27	NM_001413268.1 link	c.-315+66dupG	intron_variant	Intron 1 of 5	NP_001400197.1
CD27-AS1	NR_015382.2 link	n.1517-948dupC	intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CD27-AS1	ENST00000399492.6 link	n.485-948_485-947insC	intron_variant	Intron 5 of 6	1
CD27-AS1	ENST00000417058.6 link	n.814-948_814-947insC	intron_variant	Intron 1 of 2	1
CD27-AS1	ENST00000537003.2 link	n.1980-948_1980-947insC	intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.275

AC:

19469

AN:

70710

Hom.:

1861

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.423

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.300

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.275

AC:

19474

AN:

70720

Hom.:

1866

Cov.:

AF XY:

0.272

AC XY:

8793

AN XY:

32270

show subpopulations

African (AFR)

AF:

0.177

AC:

2728

AN:

15406

American (AMR)

AF:

0.340

AC:

2124

AN:

6250

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

720

AN:

1916

East Asian (EAS)

AF:

0.423

AC:

823

AN:

1944

South Asian (SAS)

AF:

0.194

AC:

362

AN:

1864

European-Finnish (FIN)

AF:

0.307

AC:

926

AN:

3012

Middle Eastern (MID)

AF:

0.299

AC:

AN:

144

European-Non Finnish (NFE)

AF:

0.289

AC:

11195

AN:

38686

Other (OTH)

AF:

0.302

AC:

274

AN:

906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

724

1449

2173

2898

3622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 19, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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ENST00000399492.6:n.485-948_485-947insC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over