8-23034761-T-C

Position:

• chr8-23034761-T-C

Variant summary

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

The NM_003842.5(TNFRSF10B):​c.251-3889A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 152,184 control chromosomes in the GnomAD database, including 14,200 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 0.40 (14200 hom., cov: 33)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF10B	NM_003842.5	c.251-3889A>G		intron_variant		ENST00000276431.9
TNFRSF10B	NM_147187.3	c.251-3889A>G		intron_variant
TNFRSF10B	NR_027140.2	n.282-3889A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.251-3889A>G		intron_variant		1	NM_003842.5	P2
TNFRSF10B	ENST00000347739.3	c.251-3889A>G		intron_variant		1		A2
TNFRSF10B	ENST00000523504.5	c.145-3889A>G		intron_variant, NMD_transcript_variant		2
TNFRSF10B	ENST00000519910.1	n.258-3889A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.404 AC: 61400 AN: 152066 Hom.: 14196 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.404 AC: 61426 AN: 152184 Hom.: 14200 Cov.: 33 AF XY: 0.406 AC XY: 30169 AN XY: 74396

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.413

Alfa AF: 0.488 Hom.: 23996

Bravo AF: 0.384

Asia WGS AF: 0.355 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.43

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: rs11785599; hg19: chr8-22892274;