15-40104325-C-A

Variant names:

• chr15-40104325-C-A
• rs764497660
• NM_001003940.2:c.308G>T

Variant summary

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

The NM_001003940.2(BMF):​c.308G>T​(p.Arg103Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BMF NM_001003940.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.42
• Publications: 0 publications found

Genes affected

BMF (HGNC:24132): (Bcl2 modifying factor) The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein contains a single BCL2 homology domain 3 (BH3), and has been shown to bind BCL2 proteins and function as an apoptotic activator. This protein is found to be sequestered to myosin V motors by its association with dynein light chain 2, which may be important for sensing intracellular damage and triggering apoptosis. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003940.2. 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
	BMF	NM_001003940.2	MANE Select	c.308G>T	p.Arg103Leu	missense	Exon 4 of 5	NP_001003940.1	Q96LC9-1
	BMF	NM_001398495.1		c.308G>T	p.Arg103Leu	missense	Exon 4 of 5	NP_001385424.1	Q96LC9-1
	BMF	NM_001398496.1		c.308G>T	p.Arg103Leu	missense	Exon 3 of 4	NP_001385425.1	Q96LC9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMF	ENST00000354670.9	TSL:1 MANE Select	c.308G>T	p.Arg103Leu	missense	Exon 4 of 5	ENSP00000346697.4	Q96LC9-1
	BMF	ENST00000397573.5	TSL:1	c.308G>T	p.Arg103Leu	missense	Exon 3 of 4	ENSP00000380703.1	Q96LC9-1
	BMF	ENST00000561282.5	TSL:1	c.308G>T	p.Arg103Leu	missense	Exon 3 of 4	ENSP00000453522.1	Q96LC9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.23
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0037	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.4
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.19
Sift	Benign	0.15	T
Sift4G	Benign	0.19	T
Polyphen		0.18	B
Vest4		0.71
MutPred		0.62		Gain of stability (P = 0.0114)
MVP		0.53
MPC		0.42
ClinPred		0.94	D
GERP RS		5.9
Varity_R		0.26
gMVP		0.57
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs764497660; hg19: chr15-40396526;