Genetic Variant ENST00000399492.6:n.485-909G>T (chr12-6444626-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000399492.6(CD27-AS1):n.485-909G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.021 ( 98 hom., cov: 20)

Consequence

CD27-AS1
ENST00000399492.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.72

Publications

1 publications found

Variant links:

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
CD27	NM_001413266.1 link	c.-315+507C>A	intron_variant	Intron 1 of 5	NP_001400195.1
CD27	NM_001413267.1 link	c.-403+507C>A	intron_variant	Intron 1 of 6	NP_001400196.1
CD27	NM_001413268.1 link	c.-315+19C>A	intron_variant	Intron 1 of 5	NP_001400197.1
CD27-AS1	NR_015382.2 link	n.1517-909G>T	intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CD27-AS1	ENST00000399492.6 link	n.485-909G>T	intron_variant	Intron 5 of 6	1
CD27-AS1	ENST00000417058.6 link	n.814-909G>T	intron_variant	Intron 1 of 2	1
CD27-AS1	ENST00000537003.2 link	n.1980-909G>T	intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.0211

AC:

2766

AN:

131298

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0761

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0118

Gnomad ASJ

AF:

0.00118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0135

Gnomad NFE

AF:

0.000510

Gnomad OTH

AF:

0.0158

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

GnomAD4 genome

AF:

0.0212

AC:

2780

AN:

131340

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1278

AN XY:

61854

show subpopulations

African (AFR)

AF:

0.0763

AC:

2581

AN:

33812

American (AMR)

AF:

0.0118

AC:

132

AN:

11180

Ashkenazi Jewish (ASJ)

AF:

0.00118

AC:

AN:

3380

East Asian (EAS)

AF:

0.00

AC:

AN:

4408

South Asian (SAS)

AF:

0.00

AC:

AN:

4126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6952

Middle Eastern (MID)

AF:

0.0142

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.000510

AC:

AN:

64684

Other (OTH)

AF:

0.0157

AC:

AN:

1720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

106

211

317

422

528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

122

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.074

(source)

DANN

Benign

0.21

PhyloP100

-1.7

PromoterAI

0.037

Neutral

(source)

Splicing

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

Publications

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ENST00000399492.6:n.485-909G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over