rs976881

Variant names:

• chr1-12173697-T-A
• rs976881
• NM_001066.3:c.78+6528T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-12173697-T-A
• chr1-12173697-T-C
• chr1-12173697-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001066.3(TNFRSF1B):​c.78+6528T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: TNFRSF1B NM_001066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.697
• Publications: 46 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF1B	NM_001066.3	c.78+6528T>A		intron_variant	Intron 1 of 9	ENST00000376259.7	NP_001057.1
TNFRSF1B	XM_011542060.3	c.78+6528T>A		intron_variant	Intron 1 of 10		XP_011540362.1
TNFRSF1B	XM_047429422.1	c.78+6528T>A		intron_variant	Intron 1 of 10		XP_047285378.1
TNFRSF1B	XM_011542063.3	c.78+6528T>A		intron_variant	Intron 1 of 9		XP_011540365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNFRSF1B	ENST00000376259.7	c.78+6528T>A		intron_variant	Intron 1 of 9	1	NM_001066.3	ENSP00000365435.3
TNFRSF1B	ENST00000536782.2	c.78+6528T>A		intron_variant	Intron 1 of 4	1		ENSP00000440425.1
TNFRSF1B	ENST00000492361.1	n.167+6528T>A		intron_variant	Intron 1 of 8	1
ENSG00000296888	ENST00000743341.1	n.-232T>A		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.71
DANN	Benign	0.55
PhyloP100		-0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs976881; hg19: chr1-12233754;