chr1-12182401-T-C

Position:

• chr1-12182401-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.79-6395T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,142 control chromosomes in the GnomAD database, including 3,736 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 0.22 (3736 hom., cov: 32)
• Consequence: TNFRSF1B NM_001066.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

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 (SAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNFRSF1B	NM_001066.3	c.79-6395T>C		intron_variant		ENST00000376259.7
TNFRSF1B	XM_011542060.3	c.79-6395T>C		intron_variant
TNFRSF1B	XM_011542063.3	c.79-6395T>C		intron_variant
TNFRSF1B	XM_047429422.1	c.79-6395T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNFRSF1B	ENST00000376259.7	c.79-6395T>C		intron_variant		1	NM_001066.3	P1
TNFRSF1B	ENST00000536782.2	c.79-6395T>C		intron_variant		1
TNFRSF1B	ENST00000492361.1	n.168-8556T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33163 AN: 152024 Hom.: 3723 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.218 AC: 33208 AN: 152142 Hom.: 3736 Cov.: 32 AF XY: 0.215 AC XY: 15994 AN XY: 74386

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.244

Gnomad4 OTH AF: 0.220

Alfa AF: 0.238 Hom.: 2249

Bravo AF: 0.211

Asia WGS AF: 0.206 AC: 718 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	3.0
DANN	Benign	0.62

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: rs6697733; hg19: chr1-12242458; COSMIC: COSV66163831;