chr1-12173697-T-C

Position:

• chr1-12173697-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001066.3(TNFRSF1B):​c.78+6528T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 152,110 control chromosomes in the GnomAD database, including 39,398 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 0.72 (39398 hom., cov: 32)
• Consequence: TNFRSF1B NM_001066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.697

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF1B	NM_001066.3	c.78+6528T>C		intron_variant		ENST00000376259.7
TNFRSF1B	XM_011542060.3	c.78+6528T>C		intron_variant
TNFRSF1B	XM_011542063.3	c.78+6528T>C		intron_variant
TNFRSF1B	XM_047429422.1	c.78+6528T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF1B	ENST00000376259.7	c.78+6528T>C		intron_variant		1	NM_001066.3	P1
TNFRSF1B	ENST00000536782.2	c.78+6528T>C		intron_variant		1
TNFRSF1B	ENST00000492361.1	n.167+6528T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.717 AC: 109020 AN: 151992 Hom.: 39365 Cov.: 32

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.717 AC: 109116 AN: 152110 Hom.: 39398 Cov.: 32 AF XY: 0.719 AC XY: 53449 AN XY: 74348

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.731

Alfa AF: 0.690 Hom.: 47934

Bravo AF: 0.722

Asia WGS AF: 0.732 AC: 2546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.86
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs976881; hg19: chr1-12233754;