Variant 2-32414970-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_016252.4(BIRC6):c.1679A>C(p.His560Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00342 in 1,614,004 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 12 hom. )

Consequence

BIRC6
NM_016252.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.93

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053548515).

BP6

Variant 2-32414970-A-C is Benign according to our data. Variant chr2-32414970-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 717018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd at 376 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BIRC6	NM_016252.4 linkuse as main transcript	c.1679A>C	p.His560Pro	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.1679A>C	p.His560Pro	missense_variant	10/74	1	NM_016252.4	P2
BIRC6	ENST00000700518.1 linkuse as main transcript	c.1679A>C	p.His560Pro	missense_variant	10/73			A2
BIRC6	ENST00000700519.1 linkuse as main transcript	c.1679A>C	p.His560Pro	missense_variant	10/74
BIRC6	ENST00000648282.1 linkuse as main transcript	c.1517A>C	p.His506Pro	missense_variant	10/58

Frequencies

GnomAD3 genomes

AF:

0.00247

AC:

376

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000916

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00348

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00292

AC:

732

AN:

250976

Hom.:

AF XY:

0.00279

AC XY:

378

AN XY:

135664

show subpopulations

Gnomad AFR exome

AF:

0.000802

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00231

Gnomad NFE exome

AF:

0.00409

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00352

AC:

5141

AN:

1461636

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

2488

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.0164

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00232

Gnomad4 NFE exome

AF:

0.00385

Gnomad4 OTH exome

AF:

0.00379

GnomAD4 genome

AF:

0.00247

AC:

376

AN:

152368

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00348

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00382

Hom.:

Bravo

AF:

0.00263

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00299

AC:

363

EpiCase

AF:

0.00360

EpiControl

AF:

0.00332

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

BIRC6-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

May 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

Cadd

Benign

Dann

Benign

0.95

Eigen

Benign

-0.15

Eigen_PC

Benign

0.049

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.017

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.79

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.33

Sift

Benign

0.040

Sift4G

Uncertain

0.013

Vest4

0.49

MVP

0.71

MPC

0.27

ClinPred

0.038

GERP RS

3.8

gMVP

0.53

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

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