chr12-6451407-G-T

Variant names:

• chr12-6451407-G-T
• rs1059501
• NM_001242.5:c.*15G>T

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.*15G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 1,609,634 control chromosomes in the GnomAD database, including 244,096 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (16529 hom., cov: 32)
  • Exomes 𝑓: 0.55 (227567 hom.)
• Consequence: CD27 NM_001242.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.133
• Publications: 20 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)

TAPBPL (HGNC:30683): (TAP binding protein like) Tapasin, or TAPBP (MIM 601962), is a member of the variable-constant Ig superfamily that links major histocompatibility complex (MHC) class I molecules to the transporter associated with antigen processing (TAP; see MIM 170260) in the endoplasmic reticulum (ER). The TAPBP gene is located near the MHC complex on chromosome 6p21.3. TAPBPL is a member of the Ig superfamily that is localized on chromosome 12p13.3, a region somewhat paralogous to the MHC.[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-6451407-G-T is Benign according to our data. Variant chr12-6451407-G-T is described in ClinVar as Benign. ClinVar VariationId is 402518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD27	NM_001242.5	c.*15G>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000266557.4	NP_001233.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD27	ENST00000266557.4	c.*15G>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_001242.5	ENSP00000266557.3

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63476 AN: 151894 Hom.: 16523 Cov.: 32

Gnomad AFR AF: 0.0992

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.407

GnomAD2 exomes AF: 0.494 AC: 121720 AN: 246466 AF XY: 0.510

Gnomad AFR exome AF: 0.0905

Gnomad AMR exome AF: 0.375

Gnomad ASJ exome AF: 0.485

Gnomad EAS exome AF: 0.435

Gnomad FIN exome AF: 0.578

Gnomad NFE exome AF: 0.563

Gnomad OTH exome AF: 0.513

GnomAD4 exome AF: 0.551 AC: 803868 AN: 1457622 Hom.: 227567 Cov.: 44 AF XY: 0.554 AC XY: 401779 AN XY: 725092

African (AFR) AF: 0.0811 AC: 2709 AN: 33422

American (AMR) AF: 0.376 AC: 16698 AN: 44408

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 12440 AN: 25928

East Asian (EAS) AF: 0.477 AC: 18938 AN: 39680

South Asian (SAS) AF: 0.576 AC: 49538 AN: 86014

European-Finnish (FIN) AF: 0.575 AC: 30360 AN: 52814

Middle Eastern (MID) AF: 0.443 AC: 2140 AN: 4832

European-Non Finnish (NFE) AF: 0.576 AC: 640094 AN: 1110414

Other (OTH) AF: 0.515 AC: 30951 AN: 60110

GnomAD4 genome AF: 0.418 AC: 63481 AN: 152012 Hom.: 16529 Cov.: 32 AF XY: 0.419 AC XY: 31146 AN XY: 74298

African (AFR) AF: 0.0989 AC: 4105 AN: 41492

American (AMR) AF: 0.408 AC: 6233 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1672 AN: 3472

East Asian (EAS) AF: 0.439 AC: 2260 AN: 5152

South Asian (SAS) AF: 0.566 AC: 2727 AN: 4814

European-Finnish (FIN) AF: 0.577 AC: 6091 AN: 10554

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38824 AN: 67944

Other (OTH) AF: 0.413 AC: 872 AN: 2110

Alfa AF: 0.491 Hom.: 11880

Bravo AF: 0.385

Asia WGS AF: 0.452 AC: 1571 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 59. Only high quality variants are reported. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lymphoproliferative syndrome 2 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.74
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1059501; hg19: chr12-6560573; COSMIC: COSV56945799; COSMIC: COSV56945799;