12-6444664-TGG-TGGGG

Variant names:

• chr12-6444664-T-TGG
• rs57782770
• ENST00000399492.6:n.485-948_485-947insCC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001413266.1(CD27):​c.-315+553_-315+554dupGG variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.021 (33 hom., cov: 0)
• Consequence: CD27 NM_001413266.1 intron
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD27	NM_001413266.1	c.-315+553_-315+554dupGG		intron_variant	Intron 1 of 5		NP_001400195.1
CD27	NM_001413267.1	c.-403+553_-403+554dupGG		intron_variant	Intron 1 of 6		NP_001400196.1
CD27	NM_001413268.1	c.-315+65_-315+66dupGG		intron_variant	Intron 1 of 5		NP_001400197.1
CD27-AS1	NR_015382.2	n.1517-949_1517-948dupCC		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD27-AS1	ENST00000399492.6	n.485-948_485-947insCC		intron_variant	Intron 5 of 6	1
CD27-AS1	ENST00000417058.6	n.814-948_814-947insCC		intron_variant	Intron 1 of 2	1
CD27-AS1	ENST00000537003.2	n.1980-948_1980-947insCC		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 1502 AN: 71024 Hom.: 32 Cov.: 0

Gnomad AFR AF: 0.0817

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0127

Gnomad ASJ AF: 0.00207

Gnomad EAS AF: 0.00152

Gnomad SAS AF: 0.00267

Gnomad FIN AF: 0.00296

Gnomad MID AF: 0.0260

Gnomad NFE AF: 0.00319

Gnomad OTH AF: 0.0152

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

GnomAD4 genome AF: 0.0212 AC: 1505 AN: 71038 Hom.: 33 Cov.: 0 AF XY: 0.0215 AC XY: 697 AN XY: 32416

African (AFR) AF: 0.0818 AC: 1262 AN: 15420

American (AMR) AF: 0.0127 AC: 80 AN: 6294

Ashkenazi Jewish (ASJ) AF: 0.00207 AC: 4 AN: 1930

East Asian (EAS) AF: 0.00152 AC: 3 AN: 1968

South Asian (SAS) AF: 0.00267 AC: 5 AN: 1874

European-Finnish (FIN) AF: 0.00296 AC: 9 AN: 3036

Middle Eastern (MID) AF: 0.0270 AC: 4 AN: 148

European-Non Finnish (NFE) AF: 0.00319 AC: 124 AN: 38856

Other (OTH) AF: 0.0153 AC: 14 AN: 918

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.1

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;