rs62431283

Variant names:

• chr6-136261279-G-A
• rs62431283
• NM_014739.3:c.2743C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 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
• Publications: 18 publications found

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

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=0.0021844208).
• BP6: Variant 6-136261279-G-A is Benign according to our data. Variant chr6-136261279-G-A is described in ClinVar as Benign. ClinVar VariationId is 402419.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCLAF1	NM_014739.3	MANE Select	c.2743C>T	p.Arg915Cys	missense	Exon 12 of 13	NP_055554.1	Q9NYF8-1
	BCLAF1	NM_001386700.1		c.2743C>T	p.Arg915Cys	missense	Exon 13 of 14	NP_001373629.1	Q9NYF8-1
	BCLAF1	NM_001386701.1		c.2743C>T	p.Arg915Cys	missense	Exon 13 of 14	NP_001373630.1	Q9NYF8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCLAF1	ENST00000531224.6	TSL:1 MANE Select	c.2743C>T	p.Arg915Cys	missense	Exon 12 of 13	ENSP00000435210.1	Q9NYF8-1
	BCLAF1	ENST00000527759.5	TSL:1	c.2737C>T	p.Arg913Cys	missense	Exon 12 of 13	ENSP00000434826.1	Q9NYF8-2
	BCLAF1	ENST00000530767.5	TSL:1	c.2224C>T	p.Arg742Cys	missense	Exon 12 of 13	ENSP00000436501.1	Q9NYF8-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.485 AC: 73380 AN: 151426 AF XY: 0.487

Gnomad AFR exome AF: 0.462

Gnomad AMR exome AF: 0.487

Gnomad ASJ exome AF: 0.489

Gnomad EAS exome AF: 0.479

Gnomad FIN exome AF: 0.497

Gnomad NFE exome AF: 0.482

Gnomad OTH exome AF: 0.480

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000600 AC: 2 AN: 33318

American (AMR) AF: 0.00 AC: 0 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39672

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111646

Other (OTH) AF: 0.00 AC: 0 AN: 60326

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000571021), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.0816 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.371 AC: 45062

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0022	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.5
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.25
Sift	Benign	0.032	D
Sift4G	Benign	0.10	T
Polyphen		1.0	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
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

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