12-6445158-T-C

Variant names:

• chr12-6445158-T-C
• rs553686868
• NM_001242.5:c.63T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001242.5(CD27):​c.63T>C​(p.Thr21Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T21T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CD27 NM_001242.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154
• Publications: 0 publications found

Genes affected

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-AS1 (HGNC:43896): (CD27 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.154 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD27	NM_001242.5	c.63T>C	p.Thr21Thr	synonymous_variant	Exon 1 of 6	ENST00000266557.4	NP_001233.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD27	ENST00000266557.4	c.63T>C	p.Thr21Thr	synonymous_variant	Exon 1 of 6	1	NM_001242.5	ENSP00000266557.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000417 AC: 1 AN: 240078 AF XY: 0.00000768

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458326 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 725334

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 43724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110714

Other (OTH) AF: 0.00 AC: 0 AN: 60232

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.15
PromoterAI		-0.013	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs553686868; hg19: chr12-6554324;