6-136268277-G-T

Variant names:

• chr6-136268277-G-T
• rs748791032
• NM_014739.3:c.2282C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014739.3(BCLAF1):​c.2282C>A​(p.Pro761His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P761L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BCLAF1 NM_014739.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16
• Publications: 4 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15211391).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCLAF1	NM_014739.3	c.2282C>A	p.Pro761His	missense_variant	Exon 10 of 13	ENST00000531224.6	NP_055554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCLAF1	ENST00000531224.6	c.2282C>A	p.Pro761His	missense_variant	Exon 10 of 13	1	NM_014739.3	ENSP00000435210.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250730 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;.;.;.;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D;D;D;D;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T;T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.34	N;.;.;.;.;.
PhyloP100		3.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.60	N;N;N;N;N;N
REVEL	Benign	0.060
Sift	Uncertain	0.0010	D;D;D;D;D;D
Sift4G	Benign	0.16	T;T;T;T;T;T
Polyphen		0.12	B;B;.;B;B;B
Vest4		0.36
MutPred		0.27		Loss of glycosylation at P761 (P = 0.0093);.;Loss of glycosylation at P761 (P = 0.0093);.;.;.;
MVP		0.32
ClinPred		0.74	D
GERP RS		4.9
Varity_R		0.19
gMVP		0.069
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs748791032; hg19: chr6-136589415; COSMIC: COSV99219637; COSMIC: COSV99219637;