rs17820747

Positions:

• chr2-32476619-A-C
• chr2-32476619-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016252.4(BIRC6):​c.6852+275A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,098 control chromosomes in the GnomAD database, including 3,421 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 0.21 (3421 hom., cov: 32)
• Consequence: BIRC6 NM_016252.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.727

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIRC6	NM_016252.4	c.6852+275A>C		intron_variant		ENST00000421745.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIRC6	ENST00000421745.7	c.6852+275A>C		intron_variant		1	NM_016252.4	P2
BIRC6	ENST00000648282.1	c.6638+275A>C		intron_variant
BIRC6	ENST00000700518.1	c.6801+275A>C		intron_variant				A2
BIRC6	ENST00000700519.1	c.6792+275A>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31301 AN: 151980 Hom.: 3418 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.206 AC: 31318 AN: 152098 Hom.: 3421 Cov.: 32 AF XY: 0.207 AC XY: 15377 AN XY: 74338

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.0418

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.211

Alfa AF: 0.206 Hom.: 2209

Bravo AF: 0.210

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.95
DANN	Benign	0.77

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: rs17820747; hg19: chr2-32701687;