NM_016252.4:c.12592+189G>A

Variant names:

• chr2-32543730-G-A
• rs2254106
• NM_016252.4:c.12592+189G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016252.4(BIRC6):​c.12592+189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,954 control chromosomes in the GnomAD database, including 15,649 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15649 hom., cov: 32)
• Consequence: BIRC6 NM_016252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

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.12592+189G>A		intron	N/A	NP_057336.3
	BIRC6	NM_001378125.1		c.12589+189G>A		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.12592+189G>A		intron	N/A	ENSP00000393596.2
	BIRC6	ENST00000700518.1		c.12541+189G>A		intron	N/A	ENSP00000515025.1
	BIRC6	ENST00000700519.1		c.12532+189G>A		intron	N/A	ENSP00000515026.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68211 AN: 151836 Hom.: 15616 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.449 AC: 68283 AN: 151954 Hom.: 15649 Cov.: 32 AF XY: 0.445 AC XY: 33046 AN XY: 74268

African (AFR) AF: 0.544 AC: 22534 AN: 41440

American (AMR) AF: 0.383 AC: 5858 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1371 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1426 AN: 5178

South Asian (SAS) AF: 0.308 AC: 1481 AN: 4816

European-Finnish (FIN) AF: 0.432 AC: 4544 AN: 10530

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29559 AN: 67932

Other (OTH) AF: 0.432 AC: 913 AN: 2112

Alfa AF: 0.439 Hom.: 6880

Bravo AF: 0.451

Asia WGS AF: 0.274 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.37
PhyloP100		-0.056
Mutation Taster		=100/0	polymorphism (auto)

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: rs2254106; hg19: chr2-32768797;