12-6444694-A-G

Position:

• chr12-6444694-A-G

Variant summary

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

The NM_001413266.1(CD27):​c.-315+575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 148,026 control chromosomes in the GnomAD database, including 572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.074 (572 hom., cov: 28)
• Consequence: CD27 NM_001413266.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.913

Genes affected

CD27-AS1 (HGNC:):

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=-0.9).
• BP6: Variant 12-6444694-A-G is Benign according to our data. Variant chr12-6444694-A-G is described in ClinVar as [Benign]. Clinvar id is 1276346.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD27	NM_001413266.1	c.-315+575A>G		intron_variant			NP_001400195.1
CD27	NM_001413267.1	c.-403+575A>G		intron_variant			NP_001400196.1
CD27	NM_001413268.1	c.-315+87A>G		intron_variant			NP_001400197.1
CD27-AS1	NR_015382.2	n.1517-977T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD27-AS1	ENST00000399492.6	n.485-977T>C		intron_variant		1
CD27-AS1	ENST00000417058.6	n.814-977T>C		intron_variant		1
CD27-AS1	ENST00000537003.2	n.1980-977T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 10899 AN: 147934 Hom.: 570 Cov.: 28

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0155

Gnomad AMR AF: 0.0435

Gnomad ASJ AF: 0.0259

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0683

Gnomad FIN AF: 0.0809

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0434

Gnomad OTH AF: 0.0609

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

GnomAD4 genome AF: 0.0738 AC: 10919 AN: 148026 Hom.: 572 Cov.: 28 AF XY: 0.0728 AC XY: 5247 AN XY: 72056

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0434

Gnomad4 ASJ AF: 0.0259

Gnomad4 EAS AF: 0.114

Gnomad4 SAS AF: 0.0684

Gnomad4 FIN AF: 0.0809

Gnomad4 NFE AF: 0.0434

Gnomad4 OTH AF: 0.0661

Alfa AF: 0.0469 Hom.: 245

Bravo AF: 0.0803

Asia WGS AF: 0.107 AC: 372 AN: 3478

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

Jun 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3136551; hg19: chr12-6553860;