NM_001166.5:c.41C>G

Variant names:

• chr11-102349895-C-G
• rs531296011
• NM_001166.5:c.41C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001166.5(BIRC2):​c.41C>G​(p.Ser14Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S14A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: BIRC2 NM_001166.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• Publications: 3 publications found

Genes affected

BIRC2 (HGNC:590): (baculoviral IAP repeat containing 2) The protein encoded by this gene is a member of a family of proteins that inhibits apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. This encoded protein inhibits apoptosis induced by serum deprivation and menadione, a potent inducer of free radicals. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14308682).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC2	NM_001166.5	MANE Select	c.41C>G	p.Ser14Trp	missense	Exon 2 of 9	NP_001157.1	Q13490-1
	BIRC2	NM_001256163.1		c.41C>G	p.Ser14Trp	missense	Exon 2 of 9	NP_001243092.1	Q13490-1
	BIRC2	NM_001256166.2		c.-1-106C>G		intron	N/A	NP_001243095.1	Q13490-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC2	ENST00000227758.7	TSL:1 MANE Select	c.41C>G	p.Ser14Trp	missense	Exon 2 of 9	ENSP00000227758.2	Q13490-1
	BIRC2	ENST00000613397.4	TSL:1	c.41C>G	p.Ser14Trp	missense	Exon 2 of 9	ENSP00000477613.1	Q13490-1
	BIRC2	ENST00000527910.5	TSL:1	n.1770C>G		non_coding_transcript_exon	Exon 2 of 9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.23
DANN	Benign	0.61
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.45
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.046
Sift	Benign	0.082	T
Sift4G	Benign	0.078	T
Polyphen		0.89	P
Vest4		0.28
MutPred		0.46		Loss of disorder (P = 4e-04)
MVP		0.51
MPC		0.11
ClinPred		0.15	T
GERP RS		-3.9
Varity_R		0.085
gMVP		0.41
Mutation Taster		=94/6	polymorphism

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: rs531296011; hg19: chr11-102220626;