17-42815962-G-A

Variant names:

• chr17-42815962-G-A
• rs1030558715
• NM_001313998.2:c.776C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001313998.2(BECN1):​c.776C>T​(p.Thr259Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000446 in 1,613,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: BECN1 NM_001313998.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.84
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10338825).
• BP6: Variant 17-42815962-G-A is Benign according to our data. Variant chr17-42815962-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2341507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 5 AD gene.

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.776C>T	p.Thr259Met	missense	Exon 8 of 12	NP_001300927.1	A0A024R1X5
	BECN1	NM_003766.5		c.776C>T	p.Thr259Met	missense	Exon 8 of 12	NP_003757.1	A0A024R1X5
	BECN1	NM_001313999.1		c.776C>T	p.Thr259Met	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.776C>T	p.Thr259Met	missense	Exon 8 of 12	ENSP00000465364.1	Q14457
	BECN1	ENST00000361523.8	TSL:1	c.776C>T	p.Thr259Met	missense	Exon 8 of 12	ENSP00000355231.3	Q14457
	BECN1	ENST00000893295.1		c.914C>T	p.Thr305Met	missense	Exon 9 of 13	ENSP00000563354.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152146 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251396 AF XY: 0.0000147

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000458 AC: 67 AN: 1461832 Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33 AN XY: 727212

African (AFR) AF: 0.000119 AC: 4 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000531 AC: 59 AN: 1111970

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152146 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000965 Hom.: 0

Bravo AF: 0.0000378

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.046
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.73
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.071
Sift	Benign	0.37	T
Sift4G	Benign	0.24	T
Polyphen		0.0010	B
Vest4		0.18
MutPred		0.38		Gain of MoRF binding (P = 0.0832)
MVP		0.23
MPC		0.47
ClinPred		0.12	T
GERP RS		4.9
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.12
Mutation Taster		=57/43	polymorphism

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: rs1030558715; hg19: chr17-40967980;