chr2-32532171-G-GTGTGT

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_016252.4(BIRC6):​c.12291+620_12291+621insTGTGT 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 0.000054 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0011 (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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016252.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC6	NM_016252.4	MANE Select	c.12291+620_12291+621insTGTGT		intron	N/A	NP_057336.3
	MIR558	NR_030285.1		n.19_20insTGTGT		non_coding_transcript_exon	Exon 1 of 1
	BIRC6	NM_001378125.1		c.12288+620_12288+621insTGTGT		intron	N/A	NP_001365054.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC6	ENST00000421745.7	TSL:1 MANE Select	c.12291+620_12291+621insTGTGT		intron	N/A	ENSP00000393596.2
	MIR558	ENST00000384920.1	TSL:6	n.19_20insTGTGT		non_coding_transcript_exon	Exon 1 of 1
	BIRC6	ENST00000700518.1		c.12240+620_12240+621insTGTGT		intron	N/A	ENSP00000515025.1

Frequencies

GnomAD3 genomes AF: 0.0000536 AC: 8 AN: 149338 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000744

Gnomad OTH AF: 0.000487

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00115 AC: 431 AN: 376184 Hom.: 0 Cov.: 0 AF XY: 0.00102 AC XY: 218 AN XY: 214428

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

African (AFR) AF: 0.00157 AC: 16 AN: 10206

American (AMR) AF: 0.00280 AC: 100 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.000952 AC: 11 AN: 11560

East Asian (EAS) AF: 0.0000767 AC: 1 AN: 13038

South Asian (SAS) AF: 0.00100 AC: 66 AN: 66024

European-Finnish (FIN) AF: 0.000629 AC: 20 AN: 31794

Middle Eastern (MID) AF: 0.00155 AC: 2 AN: 1292

European-Non Finnish (NFE) AF: 0.00101 AC: 192 AN: 190212

Other (OTH) AF: 0.00140 AC: 23 AN: 16372

⚠️ 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 AF: 0.0000536 AC: 8 AN: 149338 Hom.: 0 Cov.: 0 AF XY: 0.0000962 AC XY: 7 AN XY: 72802

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

African (AFR) AF: 0.0000247 AC: 1 AN: 40520

American (AMR) AF: 0.00 AC: 0 AN: 15000

Ashkenazi Jewish (ASJ) AF: 0.000291 AC: 1 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5048

South Asian (SAS) AF: 0.00 AC: 0 AN: 4666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000744 AC: 5 AN: 67236

Other (OTH) AF: 0.000487 AC: 1 AN: 2052

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0162547), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.93

Splicing

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

Other links and lift over

dbSNP: rs35999329; hg19: chr2-32757238;