rs62431287

Variant names:

• chr6-136269560-C-T
• rs62431287
• NM_014739.3:c.2096G>A

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.2096G>A​(p.Arg699His) variant causes a missense change. The variant allele was found at a frequency of 0.00000807 in 1,611,612 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: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: BCLAF1 NM_014739.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 4.09
• Publications: 21 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=0.0019322932).
• BP6: Variant 6-136269560-C-T is Benign according to our data. Variant chr6-136269560-C-T is described in ClinVar as Benign. ClinVar VariationId is 402422.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.2096G>A	p.Arg699His	missense	Exon 9 of 13	NP_055554.1	Q9NYF8-1
	BCLAF1	NM_001386700.1		c.2096G>A	p.Arg699His	missense	Exon 10 of 14	NP_001373629.1	Q9NYF8-1
	BCLAF1	NM_001386701.1		c.2096G>A	p.Arg699His	missense	Exon 10 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.2096G>A	p.Arg699His	missense	Exon 9 of 13	ENSP00000435210.1	Q9NYF8-1
	BCLAF1	ENST00000527759.5	TSL:1	c.2090G>A	p.Arg697His	missense	Exon 9 of 13	ENSP00000434826.1	Q9NYF8-2
	BCLAF1	ENST00000530767.5	TSL:1	c.1577G>A	p.Arg526His	missense	Exon 9 of 13	ENSP00000436501.1	Q9NYF8-4

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151764 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.497 AC: 113151 AN: 227730 AF XY: 0.498

Gnomad AFR exome AF: 0.466

Gnomad AMR exome AF: 0.498

Gnomad ASJ exome AF: 0.497

Gnomad EAS exome AF: 0.498

Gnomad FIN exome AF: 0.500

Gnomad NFE exome AF: 0.499

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1459848 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726206

African (AFR) AF: 0.0000300 AC: 1 AN: 33360

American (AMR) AF: 0.0000450 AC: 2 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26048

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1110936

Other (OTH) AF: 0.0000166 AC: 1 AN: 60290

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151764 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74132

African (AFR) AF: 0.0000242 AC: 1 AN: 41358

American (AMR) AF: 0.00 AC: 0 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67850

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.401 Hom.: 4199

ExAC AF: 0.496 AC: 60181

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	BCLAF1-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.14
Sift	Uncertain	0.013	D
Sift4G	Benign	0.064	T
Polyphen		0.88	P
Vest4		0.52
ClinPred		0.036	T
GERP RS		5.0
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.15
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs62431287; hg19: chr6-136590698; COSMIC: COSV50356735; COSMIC: COSV50356735;