rs6557612

Variant names:

• chr8-23042120-C-G
• rs6557612
• NM_003842.5:c.250+1018G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

TNFRSF10B Gene-Disease associations (from GenCC):

• head and neck squamous cell carcinoma

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TNFRSF10B	NM_003842.5	c.250+1018G>C		intron_variant	Intron 2 of 8	ENST00000276431.9	NP_003833.4
TNFRSF10B	NM_147187.3	c.250+1018G>C		intron_variant	Intron 2 of 9		NP_671716.2
TNFRSF10B	NR_027140.2	n.282-11248G>C		intron_variant	Intron 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF10B	ENST00000276431.9	c.250+1018G>C		intron_variant	Intron 2 of 8	1	NM_003842.5	ENSP00000276431.4
TNFRSF10B	ENST00000347739.3	c.250+1018G>C		intron_variant	Intron 2 of 9	1		ENSP00000317859.3
TNFRSF10B	ENST00000519910.1	n.257+1018G>C		intron_variant	Intron 2 of 4	4
TNFRSF10B	ENST00000523504.5	n.145-11248G>C		intron_variant	Intron 1 of 8	2		ENSP00000427999.1

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

African (AFR) AF: 0.122 AC: 5063 AN: 41524

American (AMR) AF: 0.125 AC: 1919 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3470

East Asian (EAS) AF: 0.113 AC: 584 AN: 5186

South Asian (SAS) AF: 0.191 AC: 922 AN: 4826

European-Finnish (FIN) AF: 0.190 AC: 2008 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11754 AN: 67994

Other (OTH) AF: 0.147 AC: 311 AN: 2114

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
PhyloP100		-0.14
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: rs6557612; hg19: chr8-22899633;