rs5745946

Variant names:

• chr1-12166728-AGGGCAGGTGGAGGCC-A
• rs5745946
• ENST00000782365.1:n.110+667_110+681delGGCCTCCACCTGCCC

Your query was ambiguous. Multiple possible variants found:

• chr1-12166728-AGGGCAGGTGGAGGCC-A
• chr1-12166728-AGGGCAGGTGGAGGCC-AGGGCAGGTGGAGGCCGGGCAGGTGGAGGCC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000782365.1(ENSG00000301863):​n.110+667_110+681delGGCCTCCACCTGCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (6902 hom., cov: 0)
• Consequence: ENSG00000301863 ENST00000782365.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 3 publications found

Genes affected

ENSG00000301863 (HGNC:):

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]

MIR7846 (HGNC:50029): (microRNA 7846) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNFRSF1B	NM_001066.3	c.-363_-349delGGGCAGGTGGAGGCC		upstream_gene_variant		ENST00000376259.7	NP_001057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000301863	ENST00000782365.1	n.110+667_110+681delGGCCTCCACCTGCCC		intron_variant	Intron 1 of 1
TNFRSF1B	ENST00000376259.7	c.-363_-349delGGGCAGGTGGAGGCC		upstream_gene_variant		1	NM_001066.3	ENSP00000365435.3
MIR7846	ENST00000622420.1	n.-214_-200delGGGCAGGTGGAGGCC		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44681 AN: 151228 Hom.: 6891 Cov.: 0

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.296 AC: 44738 AN: 151340 Hom.: 6902 Cov.: 0 AF XY: 0.291 AC XY: 21477 AN XY: 73892

African (AFR) AF: 0.376 AC: 15498 AN: 41166

American (AMR) AF: 0.221 AC: 3368 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3468

East Asian (EAS) AF: 0.201 AC: 1030 AN: 5124

South Asian (SAS) AF: 0.229 AC: 1093 AN: 4776

European-Finnish (FIN) AF: 0.245 AC: 2575 AN: 10498

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.284 AC: 19213 AN: 67738

Other (OTH) AF: 0.300 AC: 632 AN: 2108

Alfa AF: 0.0966 Hom.: 178

Bravo AF: 0.298

Asia WGS AF: 0.217 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5745946; hg19: chr1-12226785;