6-136272597-C-G

Variant names:

• chr6-136272597-C-G
• rs797558
• NM_014739.3:c.1958+485G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014739.3(BCLAF1):​c.1958+485G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,760 control chromosomes in the GnomAD database, including 2,857 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (2857 hom., cov: 32)
• Consequence: BCLAF1 NM_014739.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

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.1958+485G>C		intron	N/A	NP_055554.1
	BCLAF1	NM_001386700.1		c.1958+485G>C		intron	N/A	NP_001373629.1
	BCLAF1	NM_001386701.1		c.1958+485G>C		intron	N/A	NP_001373630.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCLAF1	ENST00000531224.6	TSL:1 MANE Select	c.1958+485G>C		intron	N/A	ENSP00000435210.1
	BCLAF1	ENST00000527759.5	TSL:1	c.1952+485G>C		intron	N/A	ENSP00000434826.1
	BCLAF1	ENST00000530767.5	TSL:1	c.1439+485G>C		intron	N/A	ENSP00000436501.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27974 AN: 151640 Hom.: 2854 Cov.: 32

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.185 AC: 28007 AN: 151760 Hom.: 2857 Cov.: 32 AF XY: 0.182 AC XY: 13467 AN XY: 74190

African (AFR) AF: 0.284 AC: 11749 AN: 41360

American (AMR) AF: 0.131 AC: 1997 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3468

East Asian (EAS) AF: 0.155 AC: 800 AN: 5168

South Asian (SAS) AF: 0.133 AC: 644 AN: 4826

European-Finnish (FIN) AF: 0.140 AC: 1485 AN: 10584

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10208 AN: 67836

Other (OTH) AF: 0.186 AC: 392 AN: 2112

Alfa AF: 0.0793 Hom.: 93

Bravo AF: 0.189

Asia WGS AF: 0.143 AC: 501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.32
DANN	Benign	0.76
PhyloP100		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs797558; hg19: chr6-136593735;