6-136272597-C-G

Position:

• chr6-136272597-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCLAF1	NM_014739.3	c.1958+485G>C		intron_variant		ENST00000531224.6	NP_055554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCLAF1	ENST00000531224.6	c.1958+485G>C		intron_variant		1	NM_014739.3	ENSP00000435210	P4

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

Gnomad4 AFR AF: 0.284

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.186

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.32
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs797558; hg19: chr6-136593735;