chr8-23020813-G-C

Variant names:

• chr8-23020813-G-C
• rs35974498
• NM_003842.5:c.*1858C>G

Variant summary

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

The NM_003842.5(TNFRSF10B):​c.*1858C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0484 in 454,124 control chromosomes in the GnomAD database, including 668 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 0.041 (182 hom., cov: 32)
  • Exomes 𝑓: 0.052 (486 hom.)
• Consequence: TNFRSF10B NM_003842.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214
• Publications: 4 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]

RHOBTB2 (HGNC:18756): (Rho related BTB domain containing 2) The protein encoded by this gene is a small Rho GTPase and a candidate tumor suppressor. The encoded protein interacts with the cullin-3 protein, a ubiquitin E3 ligase necessary for mitotic cell division. This protein inhibits the growth and spread of some types of breast cancer. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

RHOBTB2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR, AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 64

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003842.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	NM_003842.5	MANE Select	c.*1858C>G		3_prime_UTR	Exon 9 of 9	NP_003833.4
	TNFRSF10B	NM_147187.3		c.*1858C>G		3_prime_UTR	Exon 10 of 10	NP_671716.2	O14763-2
	TNFRSF10B	NR_027140.2		n.3125C>G		non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF10B	ENST00000276431.9	TSL:1 MANE Select	c.*1858C>G		3_prime_UTR	Exon 9 of 9	ENSP00000276431.4	O14763-1
	TNFRSF10B	ENST00000523752.5	TSL:1	n.2648C>G		non_coding_transcript_exon	Exon 4 of 4
	TNFRSF10B	ENST00000931215.1		c.*1858C>G		3_prime_UTR	Exon 9 of 9	ENSP00000601274.1

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6314 AN: 152204 Hom.: 181 Cov.: 32

Gnomad AFR AF: 0.0100

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0762

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0591

Gnomad OTH AF: 0.0430

GnomAD2 exomes AF: 0.0443 AC: 5781 AN: 130506 AF XY: 0.0464

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.0224

Gnomad ASJ exome AF: 0.0684

Gnomad EAS exome AF: 0.0000959

Gnomad FIN exome AF: 0.0708

Gnomad NFE exome AF: 0.0602

Gnomad OTH exome AF: 0.0539

GnomAD4 exome AF: 0.0518 AC: 15648 AN: 301802 Hom.: 486 Cov.: 0 AF XY: 0.0520 AC XY: 8943 AN XY: 171998

African (AFR) AF: 0.0125 AC: 107 AN: 8554

American (AMR) AF: 0.0227 AC: 620 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.0668 AC: 720 AN: 10786

East Asian (EAS) AF: 0.00 AC: 0 AN: 9210

South Asian (SAS) AF: 0.0472 AC: 2816 AN: 59650

European-Finnish (FIN) AF: 0.0733 AC: 906 AN: 12366

Middle Eastern (MID) AF: 0.0635 AC: 73 AN: 1150

European-Non Finnish (NFE) AF: 0.0608 AC: 9660 AN: 158764

Other (OTH) AF: 0.0531 AC: 746 AN: 14048

GnomAD4 genome AF: 0.0415 AC: 6315 AN: 152322 Hom.: 182 Cov.: 32 AF XY: 0.0416 AC XY: 3100 AN XY: 74466

African (AFR) AF: 0.0100 AC: 416 AN: 41578

American (AMR) AF: 0.0309 AC: 473 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 241 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0431 AC: 208 AN: 4826

European-Finnish (FIN) AF: 0.0762 AC: 809 AN: 10616

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0591 AC: 4021 AN: 68010

Other (OTH) AF: 0.0425 AC: 90 AN: 2116

Alfa AF: 0.0305 Hom.: 19

Bravo AF: 0.0364

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.67
PhyloP100		-0.21
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: rs35974498; hg19: chr8-22878326;