1-12104334-G-C

Position:

• chr1-12104334-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243.5(TNFRSF8):​c.269-45G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 1,610,680 control chromosomes in the GnomAD database, including 5,224 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 0.058 (344 hom., cov: 32)
  • Exomes 𝑓: 0.080 (4880 hom.)
• Consequence: TNFRSF8 NM_001243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635

Genes affected

TNFRSF8 (HGNC:11923): (TNF receptor superfamily member 8) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is expressed by activated, but not by resting, T and B cells. TRAF2 and TRAF5 can interact with this receptor, and mediate the signal transduction that leads to the activation of NF-kappaB. This receptor is a positive regulator of apoptosis, and also has been shown to limit the proliferative potential of autoreactive CD8 effector T cells and protect the body against autoimmunity. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -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 = 0.0789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNFRSF8	NM_001243.5	c.269-45G>C		intron_variant		ENST00000263932.7	NP_001234.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNFRSF8	ENST00000263932.7	c.269-45G>C		intron_variant		1	NM_001243.5	ENSP00000263932.2
TNFRSF8	ENST00000417814.3	c.-65-45G>C		intron_variant		1		ENSP00000390650.2
TNFRSF8	ENST00000514649.5	n.*13-45G>C		intron_variant		1		ENSP00000421938.1

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 8806 AN: 152016 Hom.: 344 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0656

Gnomad ASJ AF: 0.0373

Gnomad EAS AF: 0.0666

Gnomad SAS AF: 0.0782

Gnomad FIN AF: 0.0657

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0807

Gnomad OTH AF: 0.0556

GnomAD3 exomes AF: 0.0685 AC: 17174 AN: 250806 Hom.: 662 AF XY: 0.0693 AC XY: 9398 AN XY: 135612

Gnomad AFR exome AF: 0.0130

Gnomad AMR exome AF: 0.0829

Gnomad ASJ exome AF: 0.0357

Gnomad EAS exome AF: 0.0561

Gnomad SAS exome AF: 0.0722

Gnomad FIN exome AF: 0.0671

Gnomad NFE exome AF: 0.0761

Gnomad OTH exome AF: 0.0704

GnomAD4 exome AF: 0.0798 AC: 116346 AN: 1458544 Hom.: 4880 Cov.: 30 AF XY: 0.0795 AC XY: 57727 AN XY: 725776

Gnomad4 AFR exome AF: 0.0112

Gnomad4 AMR exome AF: 0.0815

Gnomad4 ASJ exome AF: 0.0366

Gnomad4 EAS exome AF: 0.0870

Gnomad4 SAS exome AF: 0.0736

Gnomad4 FIN exome AF: 0.0672

Gnomad4 NFE exome AF: 0.0844

Gnomad4 OTH exome AF: 0.0689

GnomAD4 genome AF: 0.0578 AC: 8801 AN: 152136 Hom.: 344 Cov.: 32 AF XY: 0.0573 AC XY: 4262 AN XY: 74384

Gnomad4 AFR AF: 0.0145

Gnomad4 AMR AF: 0.0656

Gnomad4 ASJ AF: 0.0373

Gnomad4 EAS AF: 0.0664

Gnomad4 SAS AF: 0.0773

Gnomad4 FIN AF: 0.0657

Gnomad4 NFE AF: 0.0807

Gnomad4 OTH AF: 0.0550

Alfa AF: 0.0315 Hom.: 30

Bravo AF: 0.0555

Asia WGS AF: 0.0650 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.067
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs11569850; hg19: chr1-12164391; COSMIC: COSV55801164;