12-6444664-TGG-TG

Variant names:

• chr12-6444664-TG-T
• rs57782770
• ENST00000399492.6:n.485-948delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001413266.1(CD27):​c.-315+554delG 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 (1676 hom., cov: 0)
• Consequence: CD27 NM_001413266.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.06
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 12-6444664-TG-T is Benign according to our data. Variant chr12-6444664-TG-T is described in ClinVar as [Benign]. Clinvar id is 1256950.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD27-AS1	ENST00000399492.6	n.485-948delC		intron_variant	Intron 5 of 6	1
CD27-AS1	ENST00000417058.6	n.814-948delC		intron_variant	Intron 1 of 2	1
CD27-AS1	ENST00000537003.2	n.1980-948delC		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 19760 AN: 70918 Hom.: 1679 Cov.: 0

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.260

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.278 AC: 19748 AN: 70932 Hom.: 1676 Cov.: 0 AF XY: 0.277 AC XY: 8970 AN XY: 32380

African (AFR) AF: 0.259 AC: 3989 AN: 15416

American (AMR) AF: 0.214 AC: 1344 AN: 6288

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 400 AN: 1926

East Asian (EAS) AF: 0.132 AC: 260 AN: 1966

South Asian (SAS) AF: 0.395 AC: 737 AN: 1864

European-Finnish (FIN) AF: 0.251 AC: 760 AN: 3026

Middle Eastern (MID) AF: 0.250 AC: 37 AN: 148

European-Non Finnish (NFE) AF: 0.305 AC: 11844 AN: 38790

Other (OTH) AF: 0.252 AC: 230 AN: 914

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 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)

Splicing

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

Other links and lift over

dbSNP: rs57782770; hg19: chr12-6553830;