rs62431283

chr6-136261279-G-A

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.2743C>T(p.Arg915Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,806 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 Benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: BCLAF1 NM_014739.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.46

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=0.0021844208).
• BP6: Variant 6-136261279-G-A is Benign according to our data. Variant chr6-136261279-G-A is described in ClinVar as [Benign]. Clinvar id is 402419.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.2743C>T	p.Arg915Cys	missense_variant	12/13	ENST00000531224.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCLAF1	ENST00000531224.6	c.2743C>T	p.Arg915Cys	missense_variant	12/13	1	NM_014739.3	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460806 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726626

Gnomad4 AFR exome AF: 0.0000600

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.122 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.371 AC: 45062

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.093	T;.;.;.;.;.
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;.
MetaRNN	Benign	0.0022	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.032	D;T;D;D;D;T
Sift4G	Benign	0.10	T;T;T;T;T;T
Polyphen		1.0	D;D;.;D;D;D
Vest4		0.57
ClinPred		0.0081	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.040

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: rs62431283; hg19: chr6-136582417; COSMIC: COSV50356765; COSMIC: COSV50356765;