rs35999329

Variant names:

• chr2-32532171-G-GT
• rs35999329
• NM_016252.4:c.12291+620_12291+621insT

Your query was ambiguous. Multiple possible variants found:

• chr2-32532171-G-GT
• chr2-32532171-G-GTGT
• chr2-32532171-G-GTGTGT
• chr2-32532171-G-GTGTGTGT
• chr2-32532171-G-GTGTGTGTA
• chr2-32532171-G-GTGTGTGTGT
• chr2-32532171-G-GTGTGTGTGTGT
• chr2-32532171-G-GTGTGTGTGTGTGT
• chr2-32532171-G-GTGTGTGTGTGTGTGT
• chr2-32532171-G-GTGTGTGTGTGTGTGTGT
• chr2-32532171-G-GTGTGTGTGTGTGTGTGTGT
• chr2-32532171-G-GTGTGTGTGTGTGTGTGTGTGT
• chr2-32532171-G-GTGTGTGTGTGTGTGTGTGTGTGT
• chr2-32532171-G-GTGTGTGTGTGTGTGTGTGTGTGTGT
• chr2-32532171-G-GTGTGTGTGTGTGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIRC6	NM_016252.4	c.12291+620_12291+621insT		intron_variant	Intron 61 of 73	ENST00000421745.7	NP_057336.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIRC6	ENST00000421745.7	c.12291+620_12291+621insT		intron_variant	Intron 61 of 73	1	NM_016252.4	ENSP00000393596.2

Frequencies

GnomAD3 genomes AF: 0.000845 AC: 126 AN: 149050 Hom.: 0 Cov.: 0

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000585 AC: 6 AN: 10250

American (AMR) AF: 0.00157 AC: 56 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00139 AC: 16 AN: 11534

East Asian (EAS) AF: 0.000230 AC: 3 AN: 13022

South Asian (SAS) AF: 0.000667 AC: 44 AN: 65966

European-Finnish (FIN) AF: 0.00237 AC: 75 AN: 31626

Middle Eastern (MID) AF: 0.000773 AC: 1 AN: 1294

European-Non Finnish (NFE) AF: 0.000689 AC: 131 AN: 190068

Other (OTH) AF: 0.000978 AC: 16 AN: 16364

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000665 AC: 27 AN: 40602

American (AMR) AF: 0.000600 AC: 9 AN: 14990

Ashkenazi Jewish (ASJ) AF: 0.000876 AC: 3 AN: 3426

East Asian (EAS) AF: 0.000598 AC: 3 AN: 5020

South Asian (SAS) AF: 0.00237 AC: 11 AN: 4644

European-Finnish (FIN) AF: 0.00148 AC: 15 AN: 10146

Middle Eastern (MID) AF: 0.00357 AC: 1 AN: 280

European-Non Finnish (NFE) AF: 0.000760 AC: 51 AN: 67090

Other (OTH) AF: 0.00193 AC: 4 AN: 2074

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00141 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.93

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

Other links and lift over

dbSNP: rs35999329; hg19: chr2-32757238;