12-6444664-TGG-TGGGGG

Variant names:

• chr12-6444664-T-TGGG
• rs57782770
• ENST00000399492.6:n.485-948_485-947insCCC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001413266.1(CD27):​c.-315+552_-315+554dupGGG 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 0.00015 (0 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: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000155 (11/71106) while in subpopulation AFR AF = 0.000646 (10/15470). AF 95% confidence interval is 0.00035. There are 0 homozygotes in GnomAd4. There are 4 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD27	NM_001413266.1	c.-315+552_-315+554dupGGG		intron_variant	Intron 1 of 5		NP_001400195.1
CD27	NM_001413267.1	c.-403+552_-403+554dupGGG		intron_variant	Intron 1 of 6		NP_001400196.1
CD27	NM_001413268.1	c.-315+64_-315+66dupGGG		intron_variant	Intron 1 of 5		NP_001400197.1
CD27-AS1	NR_015382.2	n.1517-950_1517-948dupCCC		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_485-947insCCC		intron_variant	Intron 5 of 6	1
CD27-AS1	ENST00000417058.6	n.814-948_814-947insCCC		intron_variant	Intron 1 of 2	1
CD27-AS1	ENST00000537003.2	n.1980-948_1980-947insCCC		intron_variant	Intron 4 of 5	1

Frequencies

GnomAD3 genomes AF: 0.000155 AC: 11 AN: 71092 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000647

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000257

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000155 AC: 11 AN: 71106 Hom.: 0 Cov.: 0 AF XY: 0.000123 AC XY: 4 AN XY: 32446

African (AFR) AF: 0.000646 AC: 10 AN: 15470

American (AMR) AF: 0.00 AC: 0 AN: 6302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1930

East Asian (EAS) AF: 0.00 AC: 0 AN: 1968

South Asian (SAS) AF: 0.00 AC: 0 AN: 1874

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 148

European-Non Finnish (NFE) AF: 0.0000257 AC: 1 AN: 38866

Other (OTH) AF: 0.00 AC: 0 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;