rs11830902

Positions:

• chr12-6450164-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001242.5(CD27):​c.269-9T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,609,108 control chromosomes in the GnomAD database, including 259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (144 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (115 hom.)
• Consequence: CD27 NM_001242.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0001778
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0250

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 12-6450164-T-C is Benign according to our data. Variant chr12-6450164-T-C is described in ClinVar as [Benign]. Clinvar id is 473871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-6450164-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD27	NM_001242.5	c.269-9T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000266557.4
CD27-AS1	NR_015382.2	n.1177+177A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD27	ENST00000266557.4	c.269-9T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001242.5	P1
CD27-AS1	ENST00000689782.1	n.100+1305A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0232 AC: 3526 AN: 152108 Hom.: 143 Cov.: 32

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00811

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00652 AC: 1613 AN: 247298 Hom.: 62 AF XY: 0.00485 AC XY: 649 AN XY: 133882

Gnomad AFR exome AF: 0.0795

Gnomad AMR exome AF: 0.00478

Gnomad ASJ exome AF: 0.00735

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000985

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000586

Gnomad OTH exome AF: 0.00247

GnomAD4 exome AF: 0.00265 AC: 3861 AN: 1456882 Hom.: 115 Cov.: 32 AF XY: 0.00239 AC XY: 1730 AN XY: 724926

Gnomad4 AFR exome AF: 0.0814

Gnomad4 AMR exome AF: 0.00544

Gnomad4 ASJ exome AF: 0.00704

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000929

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000325

Gnomad4 OTH exome AF: 0.00522

GnomAD4 genome AF: 0.0232 AC: 3532 AN: 152226 Hom.: 144 Cov.: 32 AF XY: 0.0224 AC XY: 1667 AN XY: 74420

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.00804

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0133 Hom.: 24

Bravo AF: 0.0263

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000712

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Lymphoproliferative syndrome 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -

Autoinflammatory syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Aug 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.9
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
dbscSNV1_RF	Benign	0.016
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: rs11830902; hg19: chr12-6559330;