chr8-23040572-C-T

Variant names:

• chr8-23040572-C-T
• rs10090860
• NM_003842.5:c.250+2566G>A

Variant summary

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

The NM_003842.5(TNFRSF10B):​c.250+2566G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 149,038 control chromosomes in the GnomAD database, including 9,080 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 0.34 (9080 hom., cov: 29)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

Genes affected

TNFRSF10B (HGNC:11905): (TNF receptor superfamily member 10b) The protein encoded by this gene is a member of the TNF-receptor superfamily, and contains an intracellular death domain. This receptor can be activated by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL/APO-2L), and transduces an apoptosis signal. Studies with FADD-deficient mice suggested that FADD, a death domain containing adaptor protein, is required for the apoptosis mediated by this protein. Two transcript variants encoding different isoforms and one non-coding transcript have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.250+2566G>A		intron_variant	Intron 2 of 8	ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.250+2566G>A		intron_variant	Intron 2 of 9		NP_671716.2
TNFRSF10B	NR_027140.2	n.282-9700G>A		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.250+2566G>A		intron_variant	Intron 2 of 8	1	NM_003842.5	ENSP00000276431.4
TNFRSF10B	ENST00000347739.3	c.250+2566G>A		intron_variant	Intron 2 of 9	1		ENSP00000317859.3
TNFRSF10B	ENST00000519910.1	n.257+2566G>A		intron_variant	Intron 2 of 4	4
TNFRSF10B	ENST00000523504.5	n.145-9700G>A		intron_variant	Intron 1 of 8	2		ENSP00000427999.1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 50975 AN: 148944 Hom.: 9060 Cov.: 29

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.342 AC: 51037 AN: 149038 Hom.: 9080 Cov.: 29 AF XY: 0.340 AC XY: 24689 AN XY: 72572

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.341

Alfa AF: 0.212 Hom.: 468

Bravo AF: 0.346

Asia WGS AF: 0.170 AC: 589 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.040
DANN	Benign	0.35

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: rs10090860; hg19: chr8-22898085;