12-6444626-C-G

Variant names:

• chr12-6444626-C-G
• rs11569360
• ENST00000399492.6:n.485-909G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001413266.1(CD27):​c.-315+507C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (5198 hom., cov: 20)
• Consequence: CD27 NM_001413266.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.72
• Publications: 1 publications found

Genes affected

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

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 12-6444626-C-G is Benign according to our data. Variant chr12-6444626-C-G is described in ClinVar as [Benign]. Clinvar id is 1281033.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD27-AS1	ENST00000399492.6	n.485-909G>C		intron_variant	Intron 5 of 6	1
CD27-AS1	ENST00000417058.6	n.814-909G>C		intron_variant	Intron 1 of 2	1
CD27-AS1	ENST00000537003.2	n.1980-909G>C		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 38026 AN: 131000 Hom.: 5192 Cov.: 20

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.374

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.290 AC: 38058 AN: 131042 Hom.: 5198 Cov.: 20 AF XY: 0.297 AC XY: 18297 AN XY: 61704

African (AFR) AF: 0.263 AC: 8881 AN: 33768

American (AMR) AF: 0.385 AC: 4287 AN: 11146

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 990 AN: 3378

East Asian (EAS) AF: 0.352 AC: 1545 AN: 4384

South Asian (SAS) AF: 0.195 AC: 801 AN: 4102

European-Finnish (FIN) AF: 0.381 AC: 2634 AN: 6908

Middle Eastern (MID) AF: 0.377 AC: 80 AN: 212

European-Non Finnish (NFE) AF: 0.277 AC: 17861 AN: 64566

Other (OTH) AF: 0.317 AC: 544 AN: 1718

Alfa AF: 0.0957 Hom.: 122

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.070
DANN	Benign	0.42
PhyloP100		-1.7
PromoterAI		0.0098	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11569360; hg19: chr12-6553792; COSMIC: COSV56949700;