11-102331119-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001165.5(BIRC3):c.1202G>A(p.Arg401Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00798 in 1,613,750 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0054 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0082 (65 hom.)
• Consequence: BIRC3 NM_001165.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.63

Genes affected

BIRC3 (HGNC:591): (baculoviral IAP repeat containing 3) This gene encodes a member of the IAP family of proteins that inhibit apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. The encoded protein inhibits apoptosis induced by serum deprivation but does not affect apoptosis resulting from exposure to menadione, a potent inducer of free radicals. It contains 3 baculovirus IAP repeats and a ring finger domain. Transcript variants encoding the same isoform have been identified. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006362766).
• BP6: Variant 11-102331119-G-A is Benign according to our data. Variant chr11-102331119-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 773527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 826 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIRC3	NM_001165.5	c.1202G>A	p.Arg401Lys	missense_variant	6/9	ENST00000263464.9
BIRC3	NM_182962.3	c.1202G>A	p.Arg401Lys	missense_variant	7/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BIRC3	ENST00000263464.9	c.1202G>A	p.Arg401Lys	missense_variant	6/9	1	NM_001165.5	P1

Frequencies

GnomAD3 genomes AF: 0.00543 AC: 826 AN: 152118 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00825

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00816

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00588 AC: 1478 AN: 251152 Hom.: 6 AF XY: 0.00595 AC XY: 808 AN XY: 135734

Gnomad AFR exome AF: 0.00160

Gnomad AMR exome AF: 0.00324

Gnomad ASJ exome AF: 0.0166

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00402

Gnomad FIN exome AF: 0.000971

Gnomad NFE exome AF: 0.00870

Gnomad OTH exome AF: 0.00637

GnomAD4 exome AF: 0.00825 AC: 12057 AN: 1461514 Hom.: 65 Cov.: 31 AF XY: 0.00811 AC XY: 5893 AN XY: 727066

Gnomad4 AFR exome AF: 0.00182

Gnomad4 AMR exome AF: 0.00309

Gnomad4 ASJ exome AF: 0.0172

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00420

Gnomad4 FIN exome AF: 0.00109

Gnomad4 NFE exome AF: 0.00939

Gnomad4 OTH exome AF: 0.00760

GnomAD4 genome AF: 0.00543 AC: 826 AN: 152236 Hom.: 5 Cov.: 32 AF XY: 0.00493 AC XY: 367 AN XY: 74438

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.00824

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.00816

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00749 Hom.: 2

Bravo AF: 0.00529

TwinsUK AF: 0.0129 AC: 48

ALSPAC AF: 0.00882 AC: 34

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00826 AC: 71

ExAC AF: 0.00586 AC: 711

Asia WGS AF: 0.00289 AC: 10 AN: 3476

EpiCase AF: 0.00753

EpiControl AF: 0.00972

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	BIRC3: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	22
Dann	Benign	0.96
DEOGEN2	Benign	0.077	T;T;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T;.;.
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.0064	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;L;L
MutationTaster	Benign	0.96	N;N
PrimateAI	Benign	0.31	T
Sift4G	Benign	0.97	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.094
MVP		0.44
MPC		0.29
ClinPred		0.015	T
GERP RS		4.3
Varity_R		0.21
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17881197; hg19: chr11-102201850; COSMIC: COSV54816805; COSMIC: COSV54816805;