2-32532171-G-GTGTGTGT

Position:

• chr2-32532171-G-GTGTGTGT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_016252.4(BIRC6):​c.12291+620_12291+621insTGTGTGT 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 0.00012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0024 (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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC6	NM_016252.4	c.12291+620_12291+621insTGTGTGT		intron_variant		ENST00000421745.7	NP_057336.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIRC6	ENST00000421745.7	c.12291+620_12291+621insTGTGTGT		intron_variant		1	NM_016252.4	ENSP00000393596.2

Frequencies

GnomAD3 genomes AF: 0.000121 AC: 18 AN: 149338 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.000214

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000178

Gnomad OTH AF: 0.000487

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00237 AC: 893 AN: 376188 Hom.: 0 Cov.: 0 AF XY: 0.00221 AC XY: 473 AN XY: 214434

Gnomad4 AFR exome AF: 0.00333

Gnomad4 AMR exome AF: 0.00599

Gnomad4 ASJ exome AF: 0.00450

Gnomad4 EAS exome AF: 0.000614

Gnomad4 SAS exome AF: 0.00242

Gnomad4 FIN exome AF: 0.00138

Gnomad4 NFE exome AF: 0.00178

Gnomad4 OTH exome AF: 0.00208

GnomAD4 genome AF: 0.000120 AC: 18 AN: 149456 Hom.: 0 Cov.: 0 AF XY: 0.0000960 AC XY: 7 AN XY: 72926

Gnomad4 AFR AF: 0.0000492

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000291

Gnomad4 EAS AF: 0.000199

Gnomad4 SAS AF: 0.000215

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000178

Gnomad4 OTH AF: 0.000482

Alfa AF: 0.00476 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;