6-136269502-A-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2 PP2 BP4_Strong BP6_Moderate

The NM_014739.3(BCLAF1):c.2154T>G(p.Ser718Arg) variant causes a missense change. 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.24

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, BCLAF1
• BP4: Computational evidence support a benign effect (MetaRNN=0.0016816556).
• BP6: Variant 6-136269502-A-C is Benign according to our data. Variant chr6-136269502-A-C is described in ClinVar as [Benign]. Clinvar id is 3059178.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BCLAF1	NM_014739.3	c.2154T>G	p.Ser718Arg	missense_variant	9/13	ENST00000531224.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCLAF1	ENST00000531224.6	c.2154T>G	p.Ser718Arg	missense_variant	9/13	1	NM_014739.3	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.257 Hom.: 85

Bravo AF: 0.00000378

ExAC AF: 0.497 AC: 60337

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

BCLAF1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 16, 2020

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 v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.;.;.;.;.;T;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;.;D;D
MetaRNN	Benign	0.0017	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.46	N;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.3	N;N;N;N;N;N;.;N
REVEL	Benign	0.15
Sift	Uncertain	0.017	D;T;D;D;D;T;.;.
Sift4G	Uncertain	0.026	D;D;D;D;D;D;D;.
Polyphen		1.0	D;D;.;D;D;D;.;.
Vest4		0.42
MutPred		0.28		Loss of phosphorylation at S718 (P = 2e-04);.;Loss of phosphorylation at S718 (P = 2e-04);.;.;.;Loss of phosphorylation at S718 (P = 2e-04);.;
ClinPred		0.025	T
GERP RS		5.1
Varity_R		0.12
gMVP		0.36

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

Other links and lift over

dbSNP: rs62431286; hg19: chr6-136590640; COSMIC: COSV50356784; COSMIC: COSV50356784;