12-6444640-G-A

Variant names:

• chr12-6444640-G-A
• rs11569361
• ENST00000399492.6:n.485-923C>T

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+521G>A 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 0.27 (3948 hom., cov: 19)
• Consequence: CD27 NM_001413266.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.45
• Publications: 10 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=-0.87).
• BP6: Variant 12-6444640-G-A is Benign according to our data. Variant chr12-6444640-G-A is described in ClinVar as [Benign]. Clinvar id is 1228878.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD27	NM_001413266.1	c.-315+521G>A		intron_variant	Intron 1 of 5		NP_001400195.1
CD27	NM_001413267.1	c.-403+521G>A		intron_variant	Intron 1 of 6		NP_001400196.1
CD27	NM_001413268.1	c.-315+33G>A		intron_variant	Intron 1 of 5		NP_001400197.1
CD27-AS1	NR_015382.2	n.1517-923C>T		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD27-AS1	ENST00000399492.6	n.485-923C>T		intron_variant	Intron 5 of 6	1
CD27-AS1	ENST00000417058.6	n.814-923C>T		intron_variant	Intron 1 of 2	1
CD27-AS1	ENST00000537003.2	n.1980-923C>T		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 32265 AN: 121388 Hom.: 3943 Cov.: 19

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.356

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.266 AC: 32286 AN: 121458 Hom.: 3948 Cov.: 19 AF XY: 0.272 AC XY: 15386 AN XY: 56652

African (AFR) AF: 0.196 AC: 6088 AN: 30986

American (AMR) AF: 0.368 AC: 3876 AN: 10540

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 939 AN: 3240

East Asian (EAS) AF: 0.362 AC: 1380 AN: 3808

South Asian (SAS) AF: 0.229 AC: 743 AN: 3244

European-Finnish (FIN) AF: 0.328 AC: 1911 AN: 5826

Middle Eastern (MID) AF: 0.355 AC: 76 AN: 214

European-Non Finnish (NFE) AF: 0.269 AC: 16443 AN: 61186

Other (OTH) AF: 0.299 AC: 475 AN: 1586

Alfa AF: 0.258 Hom.: 9807

Bravo AF: 0.245

Asia WGS AF: 0.234 AC: 808 AN: 3468

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.48
PhyloP100		1.5
PromoterAI		-0.025	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11569361; hg19: chr12-6553806; COSMIC: COSV56949705;