Variant 2-32415172-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_016252.4(BIRC6):c.1881A>C(p.Leu627Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

BIRC6
NM_016252.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.880

Variant links:

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]

BIRC6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0240044).

BS2

High AC in GnomAd at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIRC6	NM_016252.4 linkuse as main transcript	c.1881A>C	p.Leu627Phe	missense_variant	10/74	ENST00000421745.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
BIRC6	ENST00000421745.7 linkuse as main transcript	c.1881A>C	p.Leu627Phe	missense_variant	10/74	1	NM_016252.4	P2
BIRC6	ENST00000700518.1 linkuse as main transcript	c.1881A>C	p.Leu627Phe	missense_variant	10/73			A2
BIRC6	ENST00000700519.1 linkuse as main transcript	c.1881A>C	p.Leu627Phe	missense_variant	10/74
BIRC6	ENST00000648282.1 linkuse as main transcript	c.1719A>C	p.Leu573Phe	missense_variant	10/58

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00269

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000120

AC:

AN:

251022

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1461684

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000932

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.1881A>C (p.L627F) alteration is located in exon 10 (coding exon 10) of the BIRC6 gene. This alteration results from a A to C substitution at nucleotide position 1881, causing the leucine (L) at amino acid position 627 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.043

FATHMM_MKL

Uncertain

0.83

M_CAP

Benign

0.018

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.83

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.0

REVEL

Benign

0.24

Sift

Uncertain

0.012

Sift4G

Benign

0.081

Vest4

0.37

MutPred

0.17

Gain of sheet (P = 0.039);

MVP

0.78

MPC

0.26

ClinPred

0.076

GERP RS

3.0

gMVP

0.39

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over