rs6557612

Positions:

• chr8-23042120-C-G
• chr8-23042120-C-T

Variant summary

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

The NM_003842.5(TNFRSF10B):​c.250+1018G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,208 control chromosomes in the GnomAD database, including 1,848 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 0.15 (1848 hom., cov: 32)
• Consequence: TNFRSF10B NM_003842.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF10B	NM_003842.5	c.250+1018G>C		intron_variant		ENST00000276431.9
TNFRSF10B	NM_147187.3	c.250+1018G>C		intron_variant
TNFRSF10B	NR_027140.2	n.282-11248G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.250+1018G>C		intron_variant		1	NM_003842.5	P2
TNFRSF10B	ENST00000347739.3	c.250+1018G>C		intron_variant		1		A2
TNFRSF10B	ENST00000523504.5	c.145-11248G>C		intron_variant, NMD_transcript_variant		2
TNFRSF10B	ENST00000519910.1	n.257+1018G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23130 AN: 152090 Hom.: 1849 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.152 AC: 23128 AN: 152208 Hom.: 1848 Cov.: 32 AF XY: 0.152 AC XY: 11344 AN XY: 74418

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.139

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.147

Alfa AF: 0.156 Hom.: 257

Bravo AF: 0.140

Asia WGS AF: 0.157 AC: 548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.40

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: rs6557612; hg19: chr8-22899633;