12-6444694-A-G

Variant names:

• chr12-6444694-A-G
• rs3136551
• ENST00000399492.6:n.485-977T>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+575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 148,026 control chromosomes in the GnomAD database, including 572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.074 (572 hom., cov: 28)
• Consequence: CD27 NM_001413266.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.913
• Publications: 8 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=-0.9).
• BP6: Variant 12-6444694-A-G is Benign according to our data. Variant chr12-6444694-A-G is described in ClinVar as [Benign]. Clinvar id is 1276346.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD27	NM_001413266.1	c.-315+575A>G		intron_variant	Intron 1 of 5		NP_001400195.1
CD27	NM_001413267.1	c.-403+575A>G		intron_variant	Intron 1 of 6		NP_001400196.1
CD27	NM_001413268.1	c.-315+87A>G		intron_variant	Intron 1 of 5		NP_001400197.1
CD27-AS1	NR_015382.2	n.1517-977T>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.485-977T>C		intron_variant	Intron 5 of 6	1
CD27-AS1	ENST00000417058.6	n.814-977T>C		intron_variant	Intron 1 of 2	1
CD27-AS1	ENST00000537003.2	n.1980-977T>C		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 10899 AN: 147934 Hom.: 570 Cov.: 28

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0155

Gnomad AMR AF: 0.0435

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.0809

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0434

Gnomad OTH AF: 0.0609

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

GnomAD4 genome AF: 0.0738 AC: 10919 AN: 148026 Hom.: 572 Cov.: 28 AF XY: 0.0728 AC XY: 5247 AN XY: 72056

African (AFR) AF: 0.137 AC: 5424 AN: 39556

American (AMR) AF: 0.0434 AC: 650 AN: 14970

Ashkenazi Jewish (ASJ) AF: 0.0259 AC: 89 AN: 3442

East Asian (EAS) AF: 0.114 AC: 563 AN: 4926

South Asian (SAS) AF: 0.0684 AC: 317 AN: 4634

European-Finnish (FIN) AF: 0.0809 AC: 789 AN: 9758

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0434 AC: 2930 AN: 67470

Other (OTH) AF: 0.0661 AC: 137 AN: 2074

Alfa AF: 0.0496 Hom.: 365

Bravo AF: 0.0803

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 21, 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
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.21
PhyloP100		-0.91
PromoterAI		0.12	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3136551; hg19: chr12-6553860;