NM_001242.5:c.269-9T>C

Variant names:

• chr12-6450164-T-C
• rs11830902
• NM_001242.5:c.269-9T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001242.5(CD27):​c.269-9T>C variant causes a 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 intron
• Scores: Splicing: ADA: 0.0001778
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0250
• Publications: 1 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: Benign. The variant received -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 VariationId is 473871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD27	NM_001242.5	MANE Select	c.269-9T>C		intron	N/A	NP_001233.2
	CD27	NM_001413263.1		c.362-9T>C		intron	N/A	NP_001400192.1
	CD27	NM_001413264.1		c.242-9T>C		intron	N/A	NP_001400193.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD27	ENST00000266557.4	TSL:1 MANE Select	c.269-9T>C		intron	N/A	ENSP00000266557.3
	CD27-AS1	ENST00000399492.6	TSL:1	n.145+706A>G		intron	N/A
	CD27-AS1	ENST00000504270.4	TSL:1	n.152+1305A>G		intron	N/A

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

GnomAD2 exomes AF: 0.00652 AC: 1613 AN: 247298 AF XY: 0.00485

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 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

African (AFR) AF: 0.0814 AC: 2723 AN: 33466

American (AMR) AF: 0.00544 AC: 243 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00704 AC: 183 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000929 AC: 8 AN: 86098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49752

Middle Eastern (MID) AF: 0.00486 AC: 28 AN: 5762

European-Non Finnish (NFE) AF: 0.000325 AC: 361 AN: 1111120

Other (OTH) AF: 0.00522 AC: 315 AN: 60312

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

African (AFR) AF: 0.0800 AC: 3320 AN: 41498

American (AMR) AF: 0.00804 AC: 123 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68018

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.0127 Hom.: 37

Bravo AF: 0.0263

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000763

EpiControl AF: 0.000712

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Lymphoproliferative syndrome 2 (2)
-	-	1	Autoinflammatory syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	6.9
DANN	Benign	0.81
PhyloP100		-0.025
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11830902; hg19: chr12-6559330;