chr1-12097231-T-C

Variant names:

• chr1-12097231-T-C
• rs11569835
• NM_001243.5:c.268+14T>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.268+14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,605,042 control chromosomes in the GnomAD database, including 16,135 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 0.11 (1088 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15047 hom.)
• Consequence: TNFRSF8 NM_001243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF8	NM_001243.5	c.268+14T>C		intron_variant	Intron 3 of 14	ENST00000263932.7	NP_001234.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF8	ENST00000263932.7	c.268+14T>C		intron_variant	Intron 3 of 14	1	NM_001243.5	ENSP00000263932.2
TNFRSF8	ENST00000417814.3	c.-66+14T>C		intron_variant	Intron 2 of 13	1		ENSP00000390650.2
TNFRSF8	ENST00000514649.5	n.*12+14T>C		intron_variant	Intron 2 of 13	1		ENSP00000421938.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16534 AN: 152074 Hom.: 1089 Cov.: 32

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0967

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0445

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.110 AC: 27276 AN: 247616 AF XY: 0.112

Gnomad AFR exome AF: 0.0539

Gnomad AMR exome AF: 0.0627

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.0417

Gnomad FIN exome AF: 0.100

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.119

GnomAD4 exome AF: 0.139 AC: 202061 AN: 1452850 Hom.: 15047 Cov.: 27 AF XY: 0.138 AC XY: 99806 AN XY: 723192

African (AFR) AF: 0.0545 AC: 1813 AN: 33272

American (AMR) AF: 0.0663 AC: 2963 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2792 AN: 26046

East Asian (EAS) AF: 0.0393 AC: 1556 AN: 39622

South Asian (SAS) AF: 0.0855 AC: 7361 AN: 86084

European-Finnish (FIN) AF: 0.105 AC: 5576 AN: 53236

Middle Eastern (MID) AF: 0.0717 AC: 411 AN: 5734

European-Non Finnish (NFE) AF: 0.156 AC: 171817 AN: 1104092

Other (OTH) AF: 0.129 AC: 7772 AN: 60068

GnomAD4 genome AF: 0.109 AC: 16537 AN: 152192 Hom.: 1088 Cov.: 32 AF XY: 0.106 AC XY: 7874 AN XY: 74416

African (AFR) AF: 0.0570 AC: 2370 AN: 41548

American (AMR) AF: 0.0965 AC: 1475 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 389 AN: 3468

East Asian (EAS) AF: 0.0435 AC: 225 AN: 5178

South Asian (SAS) AF: 0.0760 AC: 367 AN: 4828

European-Finnish (FIN) AF: 0.100 AC: 1064 AN: 10600

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10314 AN: 67980

Other (OTH) AF: 0.111 AC: 233 AN: 2106

Alfa AF: 0.138 Hom.: 1007

Bravo AF: 0.106

Asia WGS AF: 0.0690 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.60
PhyloP100		0.039
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: rs11569835; hg19: chr1-12157288; COSMIC: COSV55795309;