rs11569869

Variant names:

• chr1-12109238-G-A
• rs11569869
• NM_001243.5:c.422-328G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001243.5(TNFRSF8):​c.422-328G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 152,230 control chromosomes in the GnomAD database, including 39 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 0.018 (39 hom., cov: 32)
• Consequence: TNFRSF8 NM_001243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• 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=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0184 (2794/152230) while in subpopulation NFE AF = 0.0285 (1937/68010). AF 95% confidence interval is 0.0274. There are 39 homozygotes in GnomAd4. There are 1343 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243.5. 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
	TNFRSF8	NM_001243.5	MANE Select	c.422-328G>A		intron	N/A	NP_001234.3
	TNFRSF8	NM_001281430.3		c.89-328G>A		intron	N/A	NP_001268359.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF8	ENST00000263932.7	TSL:1 MANE Select	c.422-328G>A		intron	N/A	ENSP00000263932.2
	TNFRSF8	ENST00000417814.3	TSL:1	c.89-328G>A		intron	N/A	ENSP00000390650.2
	TNFRSF8	ENST00000514649.5	TSL:1	n.*166-328G>A		intron	N/A	ENSP00000421938.1

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2794 AN: 152112 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.00524

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.0290

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0192

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

GnomAD4 genome AF: 0.0184 AC: 2794 AN: 152230 Hom.: 39 Cov.: 32 AF XY: 0.0180 AC XY: 1343 AN XY: 74436

African (AFR) AF: 0.00522 AC: 217 AN: 41546

American (AMR) AF: 0.0152 AC: 233 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

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

South Asian (SAS) AF: 0.00540 AC: 26 AN: 4818

European-Finnish (FIN) AF: 0.0290 AC: 308 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0285 AC: 1937 AN: 68010

Other (OTH) AF: 0.0190 AC: 40 AN: 2110

Alfa AF: 0.0252 Hom.: 81

Bravo AF: 0.0166

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
DANN	Benign	0.50
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

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: rs11569869; hg19: chr1-12169295;