12-6444626-C-G

Position:

• chr12-6444626-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NR_015382.2(CD27-AS1):​n.1517-909G>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (5198 hom., cov: 20)
• Consequence: CD27-AS1 NR_015382.2 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.72

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 12-6444626-C-G is Benign according to our data. Variant chr12-6444626-C-G is described in ClinVar as [Benign]. Clinvar id is 1281033.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD27-AS1	NR_015382.2	n.1517-909G>C		intron_variant, non_coding_transcript_variant
CD27	NM_001413266.1	c.-315+507C>G		intron_variant			NP_001400195.1
CD27	NM_001413267.1	c.-403+507C>G		intron_variant			NP_001400196.1
CD27	NM_001413268.1	c.-315+19C>G		intron_variant			NP_001400197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD27-AS1	ENST00000689782.1	n.460-909G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.290 AC: 38026 AN: 131000 Hom.: 5192 Cov.: 20

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.374

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.290 AC: 38058 AN: 131042 Hom.: 5198 Cov.: 20 AF XY: 0.297 AC XY: 18297 AN XY: 61704

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.381

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.317

Alfa AF: 0.0957 Hom.: 122

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.070
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11569360; hg19: chr12-6553792; COSMIC: COSV56949700;