rs2254106

Positions:

• chr2-32543730-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

BIRC6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BIRC6	NM_016252.4	c.12592+189G>A		intron_variant		ENST00000421745.7	NP_057336.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BIRC6	ENST00000421745.7	c.12592+189G>A		intron_variant		1	NM_016252.4	ENSP00000393596.2
BIRC6	ENST00000700518.1	c.12541+189G>A		intron_variant				ENSP00000515025.1
BIRC6	ENST00000700519.1	c.12532+189G>A		intron_variant				ENSP00000515026.1
BIRC6	ENST00000471232.5	n.1099+189G>A		intron_variant		2

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

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.432

Alfa AF: 0.436 Hom.: 5623

Bravo AF: 0.451

Asia WGS AF: 0.274 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.37

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: rs2254106; hg19: chr2-32768797;