17-42816018-C-A

Variant names:

• chr17-42816018-C-A
• rs1333592968
• NM_001313998.2:c.720G>T

Variant summary

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

The NM_001313998.2(BECN1):​c.720G>T​(p.Gln240His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: BECN1 NM_001313998.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36
• Publications: 0 publications found

Genes affected

BECN1 (HGNC:1034): (beclin 1) This gene encodes a protein that regulates autophagy, a catabolic process of degradation induced by starvation. The encoded protein is a component of the phosphatidylinositol-3-kinase (PI3K) complex which mediates vesicle-trafficking processes. This protein is thought to play a role in multiple cellular processes, including tumorigenesis, neurodegeneration and apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

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_001313998.2. 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
	BECN1	NM_001313998.2	MANE Select	c.720G>T	p.Gln240His	missense	Exon 8 of 12	NP_001300927.1	A0A024R1X5
	BECN1	NM_003766.5		c.720G>T	p.Gln240His	missense	Exon 8 of 12	NP_003757.1	A0A024R1X5
	BECN1	NM_001313999.1		c.720G>T	p.Gln240His	missense	Exon 7 of 10	NP_001300928.1	W0FFG4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BECN1	ENST00000590099.6	TSL:1 MANE Select	c.720G>T	p.Gln240His	missense	Exon 8 of 12	ENSP00000465364.1	Q14457
	BECN1	ENST00000361523.8	TSL:1	c.720G>T	p.Gln240His	missense	Exon 8 of 12	ENSP00000355231.3	Q14457
	BECN1	ENST00000893295.1		c.858G>T	p.Gln286His	missense	Exon 9 of 13	ENSP00000563354.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.0083	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.4
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.18
Sift	Benign	0.41	T
Sift4G	Benign	0.46	T
Polyphen		0.98	D
Vest4		0.57
MutPred		0.48		Loss of helix (P = 0.2022)
MVP		0.44
MPC		1.2
ClinPred		0.97	D
GERP RS		4.0
PromoterAI		0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.64

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: rs1333592968; hg19: chr17-40968036;