12-6448375-C-T

Variant names:

• chr12-6448375-C-T
• rs11569377
• NM_001242.5:c.269-1798C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242.5(CD27):​c.269-1798C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 152,186 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.051 (270 hom., cov: 31)
• Consequence: CD27 NM_001242.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD27	NM_001242.5	c.269-1798C>T		intron_variant	Intron 2 of 5	ENST00000266557.4	NP_001233.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD27	ENST00000266557.4	c.269-1798C>T		intron_variant	Intron 2 of 5	1	NM_001242.5	ENSP00000266557.3

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7824 AN: 152068 Hom.: 269 Cov.: 31

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00851

Gnomad FIN AF: 0.0945

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.0459

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

GnomAD4 genome AF: 0.0514 AC: 7826 AN: 152186 Hom.: 270 Cov.: 31 AF XY: 0.0505 AC XY: 3754 AN XY: 74396

African (AFR) AF: 0.0199 AC: 825 AN: 41532

American (AMR) AF: 0.0470 AC: 718 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00831 AC: 40 AN: 4816

European-Finnish (FIN) AF: 0.0945 AC: 1002 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0736 AC: 5006 AN: 67980

Other (OTH) AF: 0.0455 AC: 96 AN: 2112

Alfa AF: 0.0388 Hom.: 75

Bravo AF: 0.0470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.39
PhyloP100		-0.83
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: rs11569377; hg19: chr12-6557541;