rs597519

Variant names:

• chr1-12174828-T-C
• rs597519
• NM_001066.3:c.78+7659T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-12174828-T-C
• chr1-12174828-T-G

Variant summary

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

The NM_001066.3(TNFRSF1B):​c.78+7659T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 152,342 control chromosomes in the GnomAD database, including 97 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 0.037 (97 hom., cov: 32)
• Consequence: TNFRSF1B NM_001066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.09
• Publications: 8 publications found

Genes affected

TNFRSF1B (HGNC:11917): (TNF receptor superfamily member 1B) The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein and TNF-receptor 1 form a heterocomplex that mediates the recruitment of two anti-apoptotic proteins, c-IAP1 and c-IAP2, which possess E3 ubiquitin ligase activity. The function of IAPs in TNF-receptor signalling is unknown, however, c-IAP1 is thought to potentiate TNF-induced apoptosis by the ubiquitination and degradation of TNF-receptor-associated factor 2, which mediates anti-apoptotic signals. Knockout studies in mice also suggest a role of this protein in protecting neurons from apoptosis by stimulating antioxidative pathways. [provided by RefSeq, Jul 2008]

ENSG00000296888 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001066.3. 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
	TNFRSF1B	NM_001066.3	MANE Select	c.78+7659T>C		intron	N/A	NP_001057.1	P20333-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNFRSF1B	ENST00000376259.7	TSL:1 MANE Select	c.78+7659T>C		intron	N/A	ENSP00000365435.3	P20333-1
	TNFRSF1B	ENST00000536782.2	TSL:1	c.78+7659T>C		intron	N/A	ENSP00000440425.1	B5A977
	TNFRSF1B	ENST00000492361.1	TSL:1	n.167+7659T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0366 AC: 5566 AN: 152224 Hom.: 96 Cov.: 32

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.0136

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0133

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0315

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

GnomAD4 genome AF: 0.0366 AC: 5577 AN: 152342 Hom.: 97 Cov.: 32 AF XY: 0.0340 AC XY: 2534 AN XY: 74490

African (AFR) AF: 0.0560 AC: 2330 AN: 41576

American (AMR) AF: 0.0175 AC: 268 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 108 AN: 3470

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5190

South Asian (SAS) AF: 0.0205 AC: 99 AN: 4826

European-Finnish (FIN) AF: 0.0133 AC: 141 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0360 AC: 2451 AN: 68034

Other (OTH) AF: 0.0312 AC: 66 AN: 2116

Alfa AF: 0.0326 Hom.: 200

Bravo AF: 0.0372

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.29
PhyloP100		-4.1
Mutation Taster		=100/0	polymorphism

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: rs597519; hg19: chr1-12234885; COSMIC: COSV66163784;