rs35999329

chr2-32532171-G-GTchr2-32532171-G-GTGTchr2-32532171-G-GTGTGTchr2-32532171-G-GTGTGTGTchr2-32532171-G-GTGTGTGTGTchr2-32532171-G-GTGTGTGTGTGTchr2-32532171-G-GTGTGTGTGTGTGTchr2-32532171-G-GTGTGTGTGTGTGTGTchr2-32532171-G-GTGTGTGTGTGTGTGTGTchr2-32532171-G-GTGTGTGTGTGTGTGTGTGTchr2-32532171-G-GTGTGTGTGTGTGTGTGTGTGTchr2-32532171-G-GTGTGTGTGTGTGTGTGTGTGTGTchr2-32532171-G-GTGTGTGTGTGTGTGTGTGTGTGTGTchr2-32532171-G-GTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_016252.4(BIRC6):c.12291+620_12291+621insT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00084 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00093 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BIRC6 NM_016252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931

Genes affected

BIRC6 (HGNC:13516): (baculoviral IAP repeat containing 6) This gene encodes a protein with a BIR (baculoviral inhibition of apoptosis protein repeat) domain and a UBCc (ubiquitin-conjugating enzyme E2, catalytic) domain. This protein inhibits apoptosis by facilitating the degradation of apoptotic proteins by ubiquitination. [provided by RefSeq, Jul 2008]

MIR558 (HGNC:32814): (microRNA 558) 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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIRC6	NM_016252.4	c.12291+620_12291+621insT		intron_variant		ENST00000421745.7
MIR558	NR_030285.1	n.19_20insT		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIRC6	ENST00000421745.7	c.12291+620_12291+621insT		intron_variant		1	NM_016252.4	P2
MIR558	ENST00000384920.1	n.19_20insT		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 126 AN: 149050 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000667

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.000601

Gnomad ASJ AF: 0.000876

Gnomad EAS AF: 0.000596

Gnomad SAS AF: 0.00258

Gnomad FIN AF: 0.00148

Gnomad MID AF: 0.00333

Gnomad NFE AF: 0.000760

Gnomad OTH AF: 0.00195

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000926 AC: 348 AN: 375820 Hom.: 0 Cov.: 0 AF XY: 0.000864 AC XY: 185 AN XY: 214224

Gnomad4 AFR exome AF: 0.000585

Gnomad4 AMR exome AF: 0.00157

Gnomad4 ASJ exome AF: 0.00139

Gnomad4 EAS exome AF: 0.000230

Gnomad4 SAS exome AF: 0.000667

Gnomad4 FIN exome AF: 0.00237

Gnomad4 NFE exome AF: 0.000689

Gnomad4 OTH exome AF: 0.000978

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000838 AC: 125 AN: 149170 Hom.: 0 Cov.: 0 AF XY: 0.000893 AC XY: 65 AN XY: 72790

Gnomad4 AFR AF: 0.000665

Gnomad4 AMR AF: 0.000600

Gnomad4 ASJ AF: 0.000876

Gnomad4 EAS AF: 0.000598

Gnomad4 SAS AF: 0.00237

Gnomad4 FIN AF: 0.00148

Gnomad4 NFE AF: 0.000760

Gnomad4 OTH AF: 0.00193

Alfa AF: 0.00141 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs35999329; hg19: chr2-32757238;