12-6448026-A-T

Position:

• chr12-6448026-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242.5(CD27):​c.269-2147A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,136 control chromosomes in the GnomAD database, including 4,625 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4621 hom., cov: 31)
  • Exomes 𝑓: 0.21 (4 hom.)
• Consequence: CD27 NM_001242.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD27	NM_001242.5	c.269-2147A>T		intron_variant		ENST00000266557.4	NP_001233.2
CD27-AS1	NR_015382.2	n.1389+11T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD27	ENST00000266557.4	c.269-2147A>T		intron_variant		1	NM_001242.5	ENSP00000266557	P1
CD27-AS1	ENST00000689782.1	n.332+11T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33808 AN: 151864 Hom.: 4619 Cov.: 31

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.214 AC: 33 AN: 154 Hom.: 4 Cov.: 0 AF XY: 0.230 AC XY: 23 AN XY: 100

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.223 AC: 33826 AN: 151982 Hom.: 4621 Cov.: 31 AF XY: 0.223 AC XY: 16589 AN XY: 74282

Gnomad4 AFR AF: 0.0544

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.249

Alfa AF: 0.241 Hom.: 625

Bravo AF: 0.220

Asia WGS AF: 0.229 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2267966; hg19: chr12-6557192;