rs2754511

Variant names:

• chr2-32545090-A-T
• rs2754511
• NM_016252.4:c.12593-553A>T

Variant summary

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

The NM_016252.4(BIRC6):​c.12593-553A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,000 control chromosomes in the GnomAD database, including 5,528 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 0.24 (5528 hom., cov: 32)
• Consequence: BIRC6 NM_016252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BIRC6	NM_016252.4	c.12593-553A>T		intron_variant	Intron 62 of 73	ENST00000421745.7	NP_057336.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BIRC6	ENST00000421745.7	c.12593-553A>T		intron_variant	Intron 62 of 73	1	NM_016252.4	ENSP00000393596.2
BIRC6	ENST00000700518.1	c.12542-553A>T		intron_variant	Intron 61 of 72			ENSP00000515025.1
BIRC6	ENST00000700519.1	c.12533-553A>T		intron_variant	Intron 62 of 73			ENSP00000515026.1
BIRC6	ENST00000471232.5	n.1100-553A>T		intron_variant	Intron 5 of 17	2

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36949 AN: 151882 Hom.: 5525 Cov.: 32

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.243 AC: 36944 AN: 152000 Hom.: 5528 Cov.: 32 AF XY: 0.245 AC XY: 18203 AN XY: 74254

African (AFR) AF: 0.0612 AC: 2544 AN: 41540

American (AMR) AF: 0.265 AC: 4044 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 817 AN: 3470

East Asian (EAS) AF: 0.284 AC: 1472 AN: 5182

South Asian (SAS) AF: 0.270 AC: 1302 AN: 4818

European-Finnish (FIN) AF: 0.370 AC: 3891 AN: 10520

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21950 AN: 67866

Other (OTH) AF: 0.244 AC: 515 AN: 2112

Alfa AF: 0.276 Hom.: 769

Bravo AF: 0.227

Asia WGS AF: 0.236 AC: 818 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.9
DANN	Benign	0.59
PhyloP100		0.72
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: rs2754511; hg19: chr2-32770157;