dbSNP rs10512488: BECN1:c.1042-89C>T (chr17-42811886-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001313998.2(BECN1):c.1042-89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,480,016 control chromosomes in the GnomAD database, including 40,723 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 0.17 ( 3065 hom., cov: 32)

Exomes 𝑓: 0.23 ( 37658 hom. )

Consequence

BECN1
NM_001313998.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.132

Publications

29 publications found

Variant links:

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]

BECN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BECN1	NM_001313998.2 link	c.1042-89C>T		intron_variant	Intron 10 of 11	ENST00000590099.6	NP_001300927.1	Q14457A0A024R1X5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BECN1	ENST00000590099.6 link	c.1042-89C>T		intron_variant	Intron 10 of 11	1	NM_001313998.2	ENSP00000465364.1		Q14457

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26519

AN:

152052

Hom.:

3068

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0435

Gnomad AMI

AF:

0.293

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.0316

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.253

Gnomad OTH

AF:

0.160

GnomAD4 exome

AF:

0.230

AC:

304926

AN:

1327846

Hom.:

37658

Cov.:

AF XY:

0.227

AC XY:

149205

AN XY:

656332

show subpopulations

African (AFR)

AF:

0.0348

AC:

1025

AN:

29454

American (AMR)

AF:

0.188

AC:

5882

AN:

31294

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

4307

AN:

20598

East Asian (EAS)

AF:

0.0202

AC:

782

AN:

38656

South Asian (SAS)

AF:

0.134

AC:

9479

AN:

70826

European-Finnish (FIN)

AF:

0.252

AC:

12671

AN:

50284

Middle Eastern (MID)

AF:

0.147

AC:

650

AN:

4426

European-Non Finnish (NFE)

AF:

0.252

AC:

258646

AN:

1027022

Other (OTH)

AF:

0.208

AC:

11484

AN:

55286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

11026

22051

33077

44102

55128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8548

17096

25644

34192

42740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.174

AC:

26503

AN:

152170

Hom.:

3065

Cov.:

AF XY:

0.172

AC XY:

12777

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0433

AC:

1798

AN:

41556

American (AMR)

AF:

0.173

AC:

2649

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

771

AN:

3466

East Asian (EAS)

AF:

0.0316

AC:

164

AN:

5186

South Asian (SAS)

AF:

0.124

AC:

599

AN:

4822

European-Finnish (FIN)

AF:

0.256

AC:

2706

AN:

10566

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.253

AC:

17168

AN:

67968

Other (OTH)

AF:

0.157

AC:

332

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1082

2165

3247

4330

5412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.235

Hom.:

7655

Bravo

AF:

0.163

Asia WGS

AF:

0.0690

AC:

242

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.40

(source)

DANN

Benign

0.32

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over