Genetic Variant NM_014739.3:c.2663C>A (chr6-136261359-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014739.3(BCLAF1):c.2663C>A(p.Thr888Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

BCLAF1
NM_014739.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 8.14

Publications

24 publications found

Variant links:

Genes affected

BCLAF1 (HGNC:16863): (BCL2 associated transcription factor 1) This gene encodes a transcriptional repressor that interacts with several members of the BCL2 family of proteins. Overexpression of this protein induces apoptosis, which can be suppressed by co-expression of BCL2 proteins. The protein localizes to dot-like structures throughout the nucleus, and redistributes to a zone near the nuclear envelope in cells undergoing apoptosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

BCLAF1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004388064).

BP6

Variant 6-136261359-G-T is Benign according to our data. Variant chr6-136261359-G-T is described in ClinVar as Benign. ClinVar VariationId is 402420.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014739.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BCLAF1	NM_014739.3	MANE Select	c.2663C>A	p.Thr888Asn	missense	Exon 12 of 13	NP_055554.1
BCLAF1	NM_001386700.1		c.2663C>A	p.Thr888Asn	missense	Exon 13 of 14	NP_001373629.1
BCLAF1	NM_001386701.1		c.2663C>A	p.Thr888Asn	missense	Exon 13 of 14	NP_001373630.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BCLAF1	ENST00000531224.6	TSL:1 MANE Select	c.2663C>A	p.Thr888Asn	missense	Exon 12 of 13	ENSP00000435210.1
BCLAF1	ENST00000527759.5	TSL:1	c.2657C>A	p.Thr886Asn	missense	Exon 12 of 13	ENSP00000434826.1
BCLAF1	ENST00000530767.5	TSL:1	c.2144C>A	p.Thr715Asn	missense	Exon 12 of 13	ENSP00000436501.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.497

AC:

123282

AN:

247866

AF XY:

0.498

show subpopulations

Gnomad AFR exome

AF:

0.474

Gnomad AMR exome

AF:

0.499

Gnomad ASJ exome

AF:

0.499

Gnomad EAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.498

Gnomad OTH exome

AF:

0.499

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.904

Hom.:

40904

ExAC

AF:

0.497

AC:

60398

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency (fails inbreeding filter)

BCLAF1-related disorder

Benign:1

Apr 16, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.62

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.1

PhyloP100

8.1

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.3

REVEL

Benign

0.27

Sift

Uncertain

0.024

Sift4G

Uncertain

0.020

Polyphen

1.0

Vest4

0.92

ClinPred

0.014

GERP RS

5.5

Varity_R

0.14

gMVP

0.079

Mutation Taster

=78/22

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over