Genetic Variant NM_001313998.2: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:

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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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BECN1	NM_001313998.2	MANE Select	c.1042-89C>T	intron	N/A	NP_001300927.1	A0A024R1X5
BECN1	NM_003766.5		c.1042-89C>T	intron	N/A	NP_003757.1	A0A024R1X5
BECN1	NM_001313999.1		c.1042-958C>T	intron	N/A	NP_001300928.1	W0FFG4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BECN1	ENST00000590099.6	TSL:1 MANE Select	c.1042-89C>T	intron	N/A	ENSP00000465364.1	Q14457
BECN1	ENST00000361523.8	TSL:1	c.1042-89C>T	intron	N/A	ENSP00000355231.3	Q14457
BECN1	ENST00000893295.1		c.1180-89C>T	intron	N/A	ENSP00000563354.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over