2-32357173-T-G

Variant names:

• chr2-32357173-T-G
• rs115758817
• NM_016252.4:c.12T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_016252.4(BIRC6):​c.12T>G​(p.Gly4Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,373,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G4G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: BIRC6 NM_016252.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=0.064 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016252.4. 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
	BIRC6	NM_016252.4	MANE Select	c.12T>G	p.Gly4Gly	synonymous	Exon 1 of 74	NP_057336.3	Q9NR09
	BIRC6	NM_001378125.1		c.-73T>G		upstream_gene	N/A	NP_001365054.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BIRC6	ENST00000421745.7	TSL:1 MANE Select	c.12T>G	p.Gly4Gly	synonymous	Exon 1 of 74	ENSP00000393596.2	Q9NR09
	BIRC6	ENST00000700518.1		c.12T>G	p.Gly4Gly	synonymous	Exon 1 of 73	ENSP00000515025.1	A0A8V8TQB4
	BIRC6	ENST00000700519.1		c.12T>G	p.Gly4Gly	synonymous	Exon 1 of 74	ENSP00000515026.1	A0A8V8TR92

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373470 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 680468

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27920

American (AMR) AF: 0.00 AC: 0 AN: 31602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23916

East Asian (EAS) AF: 0.00 AC: 0 AN: 32176

South Asian (SAS) AF: 0.00 AC: 0 AN: 76686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5478

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077986

Other (OTH) AF: 0.00 AC: 0 AN: 56906

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		0.064
PromoterAI		-0.0022	Neutral
Mutation Taster		=100/0	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: rs115758817; hg19: chr2-32582241;