chr8-23022649-G-C

Variant names:

• chr8-23022649-G-C
• rs1047275
• ENST00000523752.5:n.812C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523752.5(TNFRSF10B):​n.812C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,613,034 control chromosomes in the GnomAD database, including 259,189 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 0.49 (19792 hom., cov: 30)
  • Exomes 𝑓: 0.57 (239397 hom.)
• Consequence: TNFRSF10B ENST00000523752.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• Publications: 26 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000523752.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	NM_003842.5	MANE Select	c.*22C>G		3_prime_UTR	Exon 9 of 9	NP_003833.4
	TNFRSF10B	NR_027140.2		n.1289C>G		non_coding_transcript_exon	Exon 9 of 9
	TNFRSF10B	NM_147187.3		c.*22C>G		3_prime_UTR	Exon 10 of 10	NP_671716.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	ENST00000523752.5	TSL:1	n.812C>G		non_coding_transcript_exon	Exon 4 of 4
	TNFRSF10B	ENST00000276431.9	TSL:1 MANE Select	c.*22C>G		3_prime_UTR	Exon 9 of 9	ENSP00000276431.4
	TNFRSF10B	ENST00000347739.3	TSL:1	c.*22C>G		3_prime_UTR	Exon 10 of 10	ENSP00000317859.3

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74478 AN: 151684 Hom.: 19787 Cov.: 30

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.488

GnomAD2 exomes AF: 0.538 AC: 134893 AN: 250878 AF XY: 0.537

Gnomad AFR exome AF: 0.284

Gnomad AMR exome AF: 0.519

Gnomad ASJ exome AF: 0.642

Gnomad EAS exome AF: 0.464

Gnomad FIN exome AF: 0.690

Gnomad NFE exome AF: 0.586

Gnomad OTH exome AF: 0.556

GnomAD4 exome AF: 0.568 AC: 829658 AN: 1461232 Hom.: 239397 Cov.: 38 AF XY: 0.565 AC XY: 410373 AN XY: 726924

African (AFR) AF: 0.279 AC: 9342 AN: 33468

American (AMR) AF: 0.515 AC: 22993 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 16842 AN: 26134

East Asian (EAS) AF: 0.492 AC: 19540 AN: 39694

South Asian (SAS) AF: 0.419 AC: 36110 AN: 86148

European-Finnish (FIN) AF: 0.687 AC: 36622 AN: 53336

Middle Eastern (MID) AF: 0.528 AC: 3044 AN: 5766

European-Non Finnish (NFE) AF: 0.587 AC: 652043 AN: 1111622

Other (OTH) AF: 0.549 AC: 33122 AN: 60378

GnomAD4 genome AF: 0.491 AC: 74513 AN: 151802 Hom.: 19792 Cov.: 30 AF XY: 0.493 AC XY: 36588 AN XY: 74180

African (AFR) AF: 0.290 AC: 11986 AN: 41372

American (AMR) AF: 0.484 AC: 7381 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2227 AN: 3468

East Asian (EAS) AF: 0.470 AC: 2418 AN: 5140

South Asian (SAS) AF: 0.397 AC: 1911 AN: 4812

European-Finnish (FIN) AF: 0.699 AC: 7347 AN: 10512

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39542 AN: 67934

Other (OTH) AF: 0.485 AC: 1022 AN: 2108

Alfa AF: 0.548 Hom.: 4249

Bravo AF: 0.468

Asia WGS AF: 0.405 AC: 1406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.85
DANN	Benign	0.70
PhyloP100		-0.26
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: rs1047275; hg19: chr8-22880162; COSMIC: COSV52391450; COSMIC: COSV52391450;