1-12142038-G-C

Variant names:

• chr1-12142038-G-C
• rs755398
• NM_001243.5:c.1544-249G>C

Variant summary

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

The NM_001243.5(TNFRSF8):​c.1544-249G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,960 control chromosomes in the GnomAD database, including 24,406 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 0.56 (24406 hom., cov: 32)
• Consequence: TNFRSF8 NM_001243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF8	NM_001243.5	c.1544-249G>C		intron_variant	Intron 14 of 14	ENST00000263932.7	NP_001234.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF8	ENST00000263932.7	c.1544-249G>C		intron_variant	Intron 14 of 14	1	NM_001243.5	ENSP00000263932.2

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85217 AN: 151840 Hom.: 24381 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.650

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.561 AC: 85289 AN: 151960 Hom.: 24406 Cov.: 32 AF XY: 0.555 AC XY: 41206 AN XY: 74254

African (AFR) AF: 0.590 AC: 24464 AN: 41430

American (AMR) AF: 0.423 AC: 6450 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2136 AN: 3470

East Asian (EAS) AF: 0.289 AC: 1492 AN: 5160

South Asian (SAS) AF: 0.490 AC: 2356 AN: 4812

European-Finnish (FIN) AF: 0.564 AC: 5952 AN: 10552

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40422 AN: 67958

Other (OTH) AF: 0.582 AC: 1225 AN: 2106

Alfa AF: 0.428 Hom.: 1089

Bravo AF: 0.553

Asia WGS AF: 0.393 AC: 1371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.93
DANN	Benign	0.40
PhyloP100		-0.39
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: rs755398; hg19: chr1-12202095;