Variant 19-47228208-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_014417.5(BBC3):c.224C>T(p.Ser75Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,098,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

BBC3
NM_014417.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

BBC3 (HGNC:17868): (BCL2 binding component 3) This gene encodes a member of the BCL-2 family of proteins. This family member belongs to the BH3-only pro-apoptotic subclass. The protein cooperates with direct activator proteins to induce mitochondrial outer membrane permeabilization and apoptosis. It can bind to anti-apoptotic Bcl-2 family members to induce mitochondrial dysfunction and caspase activation. Because of its pro-apoptotic role, this gene is a potential drug target for cancer therapy and for tissue injury. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

BBC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.103824675).

BP6

Variant 19-47228208-G-A is Benign according to our data. Variant chr19-47228208-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2508533.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBC3	NM_014417.5 link	c.224C>T	p.Ser75Phe	missense_variant	Exon 2 of 4	ENST00000439096.3	NP_055232.1	Q9BXH1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BBC3	ENST00000439096.3 link	c.224C>T	p.Ser75Phe	missense_variant	Exon 2 of 4	1	NM_014417.5	ENSP00000395862.2	Q9BXH1-1
BBC3	ENST00000449228.5 link	c.327C>T	p.Phe109Phe	synonymous_variant	Exon 2 of 4	1		ENSP00000404503.1	Q96PG8-2
BBC3	ENST00000341983.8 link	c.89-1454C>T		intron_variant	Intron 1 of 2	1		ENSP00000341155.4	Q9BXH1-2
BBC3	ENST00000300880.11 link	c.88+4307C>T		intron_variant	Intron 1 of 1	1		ENSP00000300880.7	Q96PG8-1

Frequencies

GnomAD3 genomes

AF:

0.00000689

AC:

AN:

145126

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:

0.000221

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000189

AC:

AN:

953082

Hom.:

Cov.:

AF XY:

0.0000157

AC XY:

AN XY:

446572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000273

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000595

Gnomad4 OTH exome

AF:

0.000255

GnomAD4 genome

AF:

0.00000689

AC:

AN:

145126

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70578

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000221

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

Asia WGS

AF:

0.000290

AC:

AN:

3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jun 02, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.38

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-2.2

REVEL

Benign

0.25

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

0.015

Vest4

0.18

MutPred

0.21

Loss of glycosylation at S75 (P = 0.0039);

MVP

0.62

ClinPred

0.19

GERP RS

2.6

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